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8.E.1.1, 1.2 Super Review
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Chapter 22 Antihypertensive Drugs Hypertension Defined (JNC-8) Pharmacology Overview 7 main categories of drugs to treat HTN Adrenergic drugs (old friend) Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers (ARBs) Calcium channel blockers (CCBs) Diuretics Vasodilators Direct renin inhibitors A. Adrenergic Drugs: 5 Subcategories and where they act A1. Adrenergic neuron blockers (central and peripheral)- we won’t talk about this A2. Alpha1 receptor blockers (peripheral) A3. Alpha2 receptor agonists (central) A4. Beta receptor blockers (peripheral) A5. Combined α and β receptor blockers (peripheral) A2. Peripherally Acting Adrenergic Drug Alpha1 Blockers (we’ve met these) Doxazosin, prazosin, alfuzosin Block alpha1-receptors which causes BP to decrease Reduces peripheral vascular resistance and BP by dilating both arterial and venous blood vessels Main Use: benign prostatic hyperplasia (BPH) Alpha1 Blockers REMEMBER Tamsulosin (Flomax)* is an α1 blocker BUT *Tamsulosin is not used to control BP, just for BPH. A3. Centrally Acting Adrenergic Drugs Alpha 2 agonist Clonidine and methyldopa 1- Stimulate alpha2-adrenergic receptors. in the brain Decreases sympathetic outflow from the CNS which decreases NE production 2. Stimulate alpha2-adrenergic receptors in kidneys remember alpha 2 opposes alpha 1 Dilates peripheral blood vessels → lowers peripheral resistance → Results in decreased BP So ….Clonidine (Catapres) Used primarily for its ability to decrease blood pressure in an urgent setting Also use in opioid withdrawal as previously discussed Oral (multiple times a day), and topical patch formulations Do not stop abruptly as it may lead to rebound hypertension In reality, Clonidine and methyldopa Not prescribed as first-line home antiHTN drugs High incidence of unwanted adverse effects: orthostatic hypotension, fatigue, and dizziness MIGHT be uses as adjunct drugs after other drugs have failed, in conjunction with other antiHTN such as diuretics A4. Adrenergic Drugs Selective Beta 1 Blockers Metoprolol, Atenolol Reduction of HR through β1 receptor blockade (remember adrenergic blocking of this receptor???) HR results in BP Cause reduced secretion of renin = BP A4. Adrenergic Drugs Selective Beta1 Blockers Nebivolol (Bystolic) Uses: hypertension and HF Action: blocks β1 receptors and produces vasodilatation, which results in a decrease in SVR High doses loses selectivity and blocks both β1 and β2 Less sexual dysfunction All BB- Do not stop abruptly; must be tapered over 1 to 2 weeks A4. Adrenergic Drugs NONSelective Beta Blockers Propranolol Acts equally on β1 and β2 Other uses include situational anxiety associated with public speaking, test taking As mentioned on previous slide, nebivolol at high doses becomes beta nonselective A5. Dual-Action Adrenergic Drugs α1 and β Receptor Blockers Dual antihypertensive effects of reduction in heart rate (beta1 receptor blockade) and vasodilation (alpha1 receptor blockade) Examples are carvedilol (common) and labetalol (not as common) A5. Dual-Action Adrenergic Drugs α1 and β Receptor Blockers Carvedilol (Coreg) Widely used drug that is well tolerated Uses: HTN, mild to moderate HF in conjunction with digoxin, diuretics, and ACE inhibitors Contraindications: severe bradycardia or unstable HF, bronchospastic conditions such as asthma, and various cardiac conduction problems Adrenergic Drugs Indications - HTN But also for Glaucoma (topical) BPH: doxazosin, prazosin, and terazosin (2 for 1) Management of severe HF when used with cardiac glycosides and diuretics Contraindications Acute HF- have to stabilize first MOAIs- yeah doesn’t everything interact with MAOIs? Peptic ulcers Severe liver/kidney disease Asthma (with beta blockers) Adrenergic Drugs: Adverse Effects Orthostatic hypotension 1st-dose syncope Rebound hypertension with abrupt discontinuation Most common: Dry mouth, drowsiness, constipation, sedation Interactions- always check for specific drug interactions Can cause additive CNS depression with alcohol, benzodiazepines, opioids Question #1 When administering an alpha-adrenergic drug for hypertension, it is most important for the nurse to assess the patient for the development of what response? Hypotension Hyperkalemia Oliguria Respiratory distress Answer A Hypotension This is a key point in patient education These drugs have strong vasodilating properties and may cause severe hypotension, especially at the beginning of therapy. B. Angiotensin-Converting Enzyme Inhibitors aka ACE Inhibitors or ACEi Large group of safe and effective drugs Currently are 10 ACEi Often used as first-line drugs for HF and hypertension May be combined with a thiazide diuretic, loop diuretic, or Calcium Channel Blocker (CCB) You need to understand the basics ACE Inhibitors: Review RAAS ACE converts angiotensin I, formed through the action of renin, to angiotensin II Angiotensin 2 is a potent vasoconstrictor and also induces aldosterone secretion by the adrenal glands Aldosterone stimulates sodium resorption (H20 follows Na Both act to raise BP which causes kidneys to reduce renin production ACEi= Great drug to treat HTN BUT contraindicated in pregnancy (2nd,3rd trimester due to fetal renal damage) and breastfeeding first few weeks after birth B. ACE Inhibitors - PRIL Lisinopril (Prinivil) super common, often the 1st drug Enalapril (Vasotec) also common Captopril (Capoten) great if liver disease present Benazepril (Lotensin) Fosinopril (Monopril) Perindopril (Aceon) Quinapril (Accupril) Ramipril (Altace) Trandolapril (Mavik) Primary Effects of the ACE Inhibitors Prevent Na (and H2O) resorption by inhibiting aldosterone secretion (volume reduction) (GO BACK TO RAAS DIAGRAM) blood volume decreases work of the heart preload, or the left ventricular end-diastolic volume which is important in HF ACE SUMMARY OF ACTIVITY 1) Prevent vasoconstriction caused by angiotensin 2 (2) Prevent aldosterone secretion less sodium and water resorption Cardioprotective Effects of ACEi They slow progression of left ventricular hypertrophy (ventricular remodeling) after MI so considered cardioprotective ACE inhibitors have been shown to decrease morbidity and mortality in patients with HF Renal Protective Effects of ACEi ACE inhibitors: reduce glomerular filtration pressure by volume reduction Cardiovascular drug of choice for patients with diabetes since it helps protect kidneys by reducing pressure. Sometimes used low dose for kidney protection with DM without HTN B. ACEi Enalapril (Vasotec) Only ACEi available in both oral and IV Enalapril IV does not require cardiac monitoring Oral enalapril: prodrug (metabolized in liver) Improves patient’s chances of survival after an MI Reduces the incidence of HF B. ACEi Captopril (Capoten) Uses: prevention of ventricular remodeling after MI; reduce the risk of HF after MI Shortest half-life Must be administered multiple times throughout the day so this limits its use Not a prodrug so good for patient with liver disease Question #2 A patient with diabetes has a new prescription for the ACE inhibitor lisinopril. She questions this order because her provider has never told her that she has hypertension. What is the best explanation for this order? The doctor knows best The patient is confused This medication has cardioprotective properties This medication has a protective effect on the kidneys for patients with diabetes Answer D ACE inhibitors have been shown to have a protective effect on the kidneys because they reduce glomerular filtration pressure. This property makes them the cardiovascular drug of choice for patients with diabetes. Question #3 A patient with a history of pancreatitis and cirrhosis is also being treated for hypertension. Which drug will most likely be ordered for this patient? Clonidine Prazosin Diltiazem Captopril Answer D Captopril Captopril is not a prodrug; therefore, it does not need to be metabolized by the liver to be effective. This is an advantage in patients with liver disease. ACE Inhibitors: Adverse Effects *Dry, nonproductive cough, which reverses when therapy is stopped. This is a class effect Dizziness- Note: First-dose hypotensive effect may occur Headache & Fatigue Possible hyperkalemia ** Angioedema: rare but potentially fatal Not safe in pregnancy-are contraindicated during the second and third trimesters of pregnancy because of increased risk of fetal renal damage C. Angiotensin II Receptor Blockers (ARB) Considered an alternative to ACEi Less likely to cause a dry cough and hyper K+ that is common with ACE inhibitors Angiotensin II Receptor Blockers: Mechanism of Action Go back to RAAS diagram! ARBs affect primarily 2 places 1. Vascular smooth muscle - blocks vasoconstriction 2. Adrenal gland -Selectively blocks the binding of Ang 2 to certain Ang 2 receptors inhibiting secretion of aldosterone Lowers volume retention and BP Angiotensin II Receptor Blockers -ARTAN Losartan (Cozaar)- very common Eprosartan (Teveten) Valsartan (Diovan) Irbesartan (Avapro) Candesartan (Atacand) Olmesartan (Benicar) Telmisartan (Micardis) Azilsartan (Edarbi) C. ARB Losartan (Cozaar) Beneficial in patients with HTN and HF Used with caution in patients with kidney or liver dysfunction and in patients with renal artery stenosis ***Not safe for breastfeeding women and should not be used in pregnancy (Cat C 1st trimester, Cat D 2nd-3rd trimester), potential fetal toxicity Appear to be equally effective for the treatment of hypertension and well tolerated ARBs less likely to cause cough and hyperK+ but can still happen Evidence that ARBs are associated with lower mortality after MI than ACE inhibitors Never take ACEi and ARBs at the same time* 5. Calcium Channel Blockers (CCB) Primary use: HTN, angina, some dysrhythmias Cause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contraction Results in: Relaxed blood vessels to the heart Decreased peripheral smooth muscle tone Decreased SVResistance Decreased BP E. Diuretics First-line antiHTN in JNC 8 guidelines Decreases fluid volume The results from diuresis: preload, Peripheral resistance Overall effect Decreased workload of the heart and decreased BP Thiazide diuretics are the most commonly used diuretics for HTN Ie hydrochlorothiazide (HCTZ), chlorthalidone We will discuss diuretics further in the chapter on diuretics F. Vasodilators Directly relax arterial or venous smooth muscle (or both) Results in: Decreased SVR Decreased afterload Peripheral vasodilation Indicated for treatment of HTN May be used in combination with other drugs F. Vasodilators Hydralazine (Apresoline) Orally: routine cases of essential hypertension Injectable: hypertensive emergencies BiDil: specifically indicated as an adjunct for treatment of HF in African-American patients F. Vasodilators Sodium Nitroprusside (Nitropress) *Sodium nitroprusside and IV diazoxide are reserved for the management of hypertensive emergencies. Contraindications: severe HF, known inadequate cerebral perfusion (especially during neurosurgical procedures) F. Vasodilators Adverse Effects Hydralazine: dizziness, headache, tachycardia, edema, dyspnea, N/V/D, vitamin B6 deficiency, rash Sodium nitroprusside: hypotension, bradycardia, decreased platelet aggregation, rash G. Direct Renin Inhibitors Aliskirin (Tekturna) Blocks the RAS pathway at the point of activation. Inhibiting renin production prevents the downstream production of Ang II (potent vasoconstrictor) Adverse effects: N/V, severe hypotension, hyponatremia, hyperkalemia… Contraindicated in patients with DM taking ACEi or ARB Miscellaneous Antihypertensives Eplerenone (Inspra) Newer class of drugs called selective aldosterone blockers (remember RAAS?) Reduces BP by blocking the actions of aldosterone at its corresponding receptors in the kidney, heart, blood vessels, and brain Indications: routine treatment of hypertension and for post-MI HF Contraindicated if serum potassium levels are high (above 5.6 mEq/L) A Special Form of HTN Treatment of Pulmonary Hypertension Sildenafil and Tadalafil Commonly used for erectile dysfunction Used for pulmonary hypertension but with different trade names Sildenafil: Revatio* (Viagra for ED) Tadalafil: Adcirca* (Cialis for ED)Owls, such as the young snowy owls on the previous page, have for centuries been symbols of both wisdom and mystery. To many cultures their piercing eyes have conveyed a look of intelligence. Their silent flight through darkened landscapes in search of prey has projected an air of power or wonder. For this chapter and this book, owls are an engaging example of a living organism from the world of biology—the study of life. BIOLOGY AND YOU Living in a small town, in the country, or at the edge of the suburbs, one may be lucky enough to hear an owl's hooting. This experience can lead to questions about where the bird lives, what it hunts, and how it finds its prey on dark, moonless nights. Biology, or the study of life, offers an organized and scientific framework for posing and answering such questions about the natural world. Biologists study questions about how living things work, how they interact with the environment, and how they change over time. Biologists study many different kinds of living things ranging from tiny organisms, such as bacteria, to very large organisms, such as elephants. Each day, biologists investigate subjects that affect you and the way you live. For example, biologists determine which foods are healthy. As shown in Figure 1-1, everyone is affected by this impor- tant topic. Biologists also study how much a person should exer- cise and how one can avoid getting sick. Biologists also study what CHARACTERISTICS OF LIFE The world is filled with familiar objects, such as tables, rocks, plants, pets, and automobiles. Which of these objects are living or were once living? What are the criteria for assigning something to the living world or the nonliving world? Biologists have established that living things share seven characteristics of life. These characteristics are organization and the presence of one or more cells, response to a stimulus (plural, stimuli), homeostasis, metabolism, growth and development, reproduction, and change through time. Organization and Cells Organization is the high degree of order within an organism’s internal and external parts and in its interactions with the living world. For example, compare an owl to a rock. The rock has a spe- cific shape, but that shape is usually irregular. Furthermore, differ- ent rocks, even rocks of the same type, are likely to have different shapes and sizes. In contrast, the owl is an amazingly organized individual, as shown in Figure 1-2. Owls of the same species have the same body parts arranged in nearly the same way and interact with the environment in the same way. Copyright © by Holt, Rinehart and Winston. All rights reserved. ORGANISM (Barn Owl) ORGAN (Owl’s Ear) TISSUE (Nervous Tissue Within the Ear) CELL (Nerve Cell) your air, land, and fAll living organisms, whether made up of one cell or many cells, have some degree of organization. A cell is the smallest unit that can perform all life’s processes. Some organisms, such as bacteria, are made up of one cell and are called unicellular (YOON-uh-SEL-yoo-luhr) organisms. Other organisms, such as humans or trees, are made up of multiple cells and are called multicellular (MUHL-ti-SEL-yoo-luhr) organisms. Complex multicellular organisms have the level of orga- nization shown in Figure 1-2. In the highest level, the organism is made up of organ systems, or groups of specialized parts that carry out a certain function in the organism. For example, an owl’s ner- vous system is made up of a brain, sense organs, nerve cells, and other parts that sense and respond to the owl’s surroundings. Organ systems are made up of organs. Organs are structures that carry out specialized jobs within an organ system. An owl’s ear is an organ that allows the owl to hear. All organs are made up of tissues. Tissues are groups of cells that have similar abilities and that allow the organ to function. For example, nervous tissue in the ear allows the ear to detect sound. Tissues are made up of cells. A cell must be covered by a membrane, contain all genetic information necessary for replication, and be able to carry out all cell functions. Within each cell are organelles. Organelles are tiny structures that carry out functions necessary for the cell to stay alive. Organelles contain biological molecules, the chemical compounds that provide physical structure and that bring about movement, energy use, and other cellular functions. All biological molecules are made up of atoms. Atoms are the simplest particle of an ele- ment that retains all the properties of a certain element. Response to Stimuli Another characteristic of life is that an organism can respond to a stimulus—a physical or chemical change in the internal or external environment. For example, an owl dilates its pupils to keep the level of light entering the eye constant. Organisms must be able to respond and react to changes in their environment to stay alive. ORGANELLE (Mitochondrion) BIOLOGICAL MOLECULE (Phospholipid) ATOM (Oxygen) cell from the Latin, cella meaning “small room,” or “hut” Word Roots and Origins www.scilinks.org Topic: Characteristics of Life Keyword: HM60257 mb06se_bios01.qxd 5/18/07 10:37 AM Page 7 8 CHAPTER 1 Homeostasis All living things, from single cells to entire organisms, have mecha- nisms that allow them to maintain stable internal conditions. Without these mechanisms, organisms can die. For example, a cell’s water content is closely controlled by the taking in or releas- ing of water. A cell that takes in too much water will rupture and die. A cell that doesn’t get enough water will also shrivel and die. Homeostasis (HOH-mee-OH-STAY-sis) is the maintenance of a stable level of internal conditions even though environmental conditions are constantly changing. Organisms have regulatory systems that maintain internal conditions, such as temperature, water content, and uptake of nutrients by the cell. In fact, multi- cellular organisms usually have more than one way of maintain- ing important aspects of their internal environment. For example, an owl’s temperature is maintained at about 40°C (104°F). To keep a constant temperature, an owl’s cells burn fuel to produce body heat. In addition, an owl’s feathers can fluff up in cold weather. In this way, they trap an insulating layer of air next to the bird’s body to maintain its body temperature. Metabolism Living organisms use energy to power all the life processes, such as repair, movement, and growth. This energy use depends on metabolism (muh-TAB-uh-LIZ-uhm). Metabolism is the sum of all the chemical reactions that take in and transform energy and materials from the environment. For example, plants, algae, and some bacteria use the sun’s energy to generate sugar molecules during a process called photosynthesis. Some organisms depend on obtaining food energy from other organisms. For instance, an owl’s metabolism allows the owl to extract and modify the chemi- cals trapped in its nightly prey and use them as energy to fuel activities and growth. Growth and Development All living things grow and increase in size. Some nonliving things, such as crystals or icicles, grow by accumulating more of the same material of which they are made. In contrast, the growth of living things results from the division and enlargement of cells. Cell division is the formation of two new cells from an existing cell, as shown in Figure 1-3. In unicellular organisms, the primary change that occurs following cell division is cell enlargement. In multi- cellular life, however, organisms mature through cell division, cell enlargement, and development. Development is the process by which an organism becomes a mature adult. Development involves cell division and cell differen- tiation, or specialization. As a result of development, an adult organism is composed of many cells specialized for different func- tions, such as carrying oxygen in the blood or hearing. In fact, the human body is composed of trillions of specialized cells, all of which originated from a single cell, the fertilized egg. This unicellular organism, Escherichia coli, inhabits the human intestines. E. coli reproduces by means of cell division, during which the original cell splits into two identical offspring cells. FIGURE 1-3 Observing Homeostasis Materials 500 mL beakers (3), wax pen, tap water, thermometer, ice, hot water, goldfish, small dip net, watch or clock with a second hand Procedure 1. Use a wax pen to label three 500 mL beakers as follows: 27°C (80°F), 20°C (68°F), 10°C (50°F). Put 250 mL of tap water in each beaker. Use hot water or ice to adjust the tem- perature of the water in each beaker to match the temperature on the label. 2. Put the goldfish in the beaker of 27°C water. Record the number of times the gills move in 1 minute. 3. Move the goldfish to the beaker of 20°C water. Repeat observations. Move the goldfish to the beaker of 10°C. Repeat observations. Analysis What happens to the rate at which gills move when the temp- erature changes? Why? How do gills help fish maintain homeostasis? Quick Lab mb06se_bios01.qxd 5/18/07 10:37 AM Page 8 THE SCIENCE OF LIFE 9 Reproduction All organisms produce new organisms like themselves in a process called reproduction. Reproduction, unlike other characteristics, is not essential to the survival of an individual organism. However, because no organism lives forever, reproduction is essential for the continuation of a species. Glass frogs, as shown in Figure 1-4, lay many eggs in their lifetime. However, only a few of the frogs’ off- spring reach adulthood and successfully reproduce. During reproduction, organisms transmit hereditary informa- tion to their offspring. Hereditary information is encoded in a large molecule called deoxyribonucleic acid, or DNA. A short segment of DNA that contains the instructions for a single trait of an organism is called a gene. DNA is like a large library. It contains all the books—genes—that the cell will ever need for making all the struc- tures and chemicals necessary for life. Hereditary information is transferred to offspring during two kinds of reproduction. In sexual reproduction, hereditary information recombines from two organisms of the same species. The resulting offspring are similar but not identical to their parents. For example, a male frog’s sperm can fertilize a female’s egg and form a single fer- tilized egg cell. The fertilized egg then develops into a new frog. In asexual reproduction, hereditary information from different organisms is not combined; thus the original organism and the new organism are genetically the same. A bacterium, for example, reproduces asexually when it splits into two identical cells. Change Through Time Although individual organisms experience many changes during their lifetime, their basic genetic characteristics do not change. However, populations of living organisms evolve or change through time. The ability of populations of organisms to change over time is important for survival in a changing world. This factor is also impor- tant in explaining the diversity of life-forms we see on Earth today. 1. How does biology affect a person’s daily life? 2. How does biology affect society? 3. Name the characteristics shared by living things. 4. Summarize the hierarchy of organization found in complex multicellular organisms. 5. What are the different functions of homeostasis and metabolism in living organisms? 6. How does the growth among living and nonliv- ing things differ? 7. Why is reproduction an important characteristic of life? CRITICAL THINKING 8. Applying Information Crystals of salt grow and are highly organized. Why don’t biologists con- sider them to be alive? 9. Analyzing Models When a scientist designs a space probe to detect life on a distant planet, what kinds of things should it measure? 10. Making Comparisons Both cells and organisms share the characteristics of life. How are cells and organismsood supply will be like in the near future.EVOLUTION OF LIFE Individual organisms change during their lifetime, but their basic genetic characteristics do not change. However, populations of liv- ing organisms do change through time, or evolve. Evolution, or descent with modification, is the process in which the inherited characteristics within populations change over generations, such that genetically distinct populations and new species can develop. Evolution as a theme in biology helps us understand how the various branches of the “tree of life” came into existence and have changed over time. It also explains how organisms alive today are related to those that lived in the past. Finally, it helps us understand the mechanisms that underlie the way organisms look and behave. Natural Selection The ability of populations of organisms to change over time is important for survival in a changing world. According to the theory of evolution by natural selection, organisms that have certain favorable traits are better able to survive and reproduce success- fully than organisms that lack these traits. One product of natural selection is the adaptation of organisms to their environment. Adaptations are traits that improve an indi- vidual’s ability to survive and reproduce. For example, rabbits with white fur and short ears in a snowy place, such as the one in Figure 1-7a, may avoid predators and frostbitten ears more often than those with dark fur and long ears. Thus, the next generation of rabbits will have a greater percentage of animals carrying the genes for white fur and short ears. In contrast, the brown, long- eared rabbit, as shown in Figure 1-7b, would survive and reproduce more successfully in a hot desert environment. The survival and reproductive success of organisms with favor- able traits cause a change in populations of organisms over gener- ations. This descent with modification is an important factor in explaining the diversity of organisms we see on Earth today. 1. Name three unifying themes found in biology. 2. How is the unity and diversity in the living world represented? 3. Identify the three domains and the kingdoms found in each domain. 4. How are organisms interdependent? 5. Describe why evolution is important in explain- ing the diversity of life. 6. Distinguish between evolution and natural selection. CRITICAL THINKING 7. Applying Information Assign the various top- pings you put on pizza to the appropriate domains and kingdoms of life. 8. Analyzing Graphics According to the “tree” in Figure 1-5, which of these pairs are more closely related: Archaea:Bacteria or Archaea:Eukarya? 9. Making Hypotheses Fossil evidence shows that bats descended from shrewlike organisms that could not fly. Write a hypothesis for how natural selection might have led to flying bats. SECTION 2 REVIEW (a) This short-eared arctic hare, Lepus arcticus, is hidden from predators and protected from frostbite in a snowy environment. (b) The mottled brown coats of desert rabbits blend in with the dirt and dry grasses, and their long ears help them radiate excess heat and thus avoid overheating. FIGURE 1-7 (a) (b) Copyright © by Holt, Rinehart and Winston. All rights reserved. THE SCIENCE OF LIFE 13 TH E STUDY OF BIOLOGY Curiosity leads us to ask questions about life. Science provides a way of answering such questions about the natural world. Science is a systematic method that involves forming and testing hypotheses. More importantly, science relies on evidence, not beliefs, for drawing conclusions. SCIENCE AS A PROCESS Science is characterized by an organized approach, called the scientific method, to learn how the natural world works. The methods of science are based on two important principles. The first principle is that events in the natural world have natural causes. For example, the ancient Greeks believed that lightning and thunder occurred because a supernatural god Zeus hurled thunderbolts from the heavens. By contrast, a scientist considers lightning and thunder to result from electric charges in the atmos- phere. When trying to solve a puzzle from nature, all scientists, such as the one in Figure 1-8, accept that there is a natural cause to solve that puzzle. A second principle of science is uniformity. Uniformity is the idea that the fundamental laws of nature operate the same way at all places and at all times. For example, scientists assume that the law of gravity works the same way on Mars as it does on Earth. Steps of the Scientific Method Although there is no single method for doing science, scientific studies involve a series of common steps. 1. The process of science begins with an observation. An observation is the act of perceiving a natural occurrence that causes someone to pose a question. 2. One tries to answer the question by forming hypotheses (singular, hypothesis). A hypothesis is a proposed explanation for the way a particular aspect of the natural world functions. 3. A prediction is a statement that forecasts what would happen in a test situation if the hypothesis were true. A prediction is recorded for each hypothesis. 4. An experiment is used to test a hypothesis and its predictions. 5. Once the experiment has been concluded, the data are analyzed and used to draw conclusions. 6. After the data have been analyzed, the data and conclusions are communicated to scientific peers and to the public. This way oth- ers can verify, reject, or modify the researcher’s conclusions. SECTION 3 OBJECTIVES ● Outline the main steps in the scientific method. ● Summarize how observations are used to form hypotheses. ● List the elements of a controlled experiment. ● Describe how scientists use data to draw conclusions. ● Compare a scientific hypothesis and a scientific theory. ● State how communication in science helps prevent dishonesty and bias. VOCABULARY scientific method observation hypothesis prediction experiment control group experimental group independent variable dependent variable theory peer review All researchers, such as the one releasing an owl above, use the scientific method to answer the questions they have about nature. FIGURE 1-8 Copyright © by Holt, Rinehart and Winston. All rights reserved. 14 CHAPTER 1 OBSERVING AND ASKING QUESTIONS The scientific method generally begins with an unexplained observa- tion about nature. For example, people have noticed for thousands of years that owls can catch prey in near total darkness. As shown in steps and of Figure 1-9, an observation may then raise ques- tions. The owl observation raises the question: How does an owl detect prey in the dark? FORMING A HYPOTHESIS After stating a question, a biologist lists possible answers to a sci- entific question—hypotheses. Good hypotheses answer a question and are testable in the natural world. For example, as shown in step Figure 1-9, there are several possible hypotheses for the question of how owls hunt at night: (a) owls hunt by keen vision in the dark; (b) owls hunt by superb hearing; or (c) owls hunt by detecting the prey’s body heat. Predicting To test a hypothesis, scientists make a prediction that logically fol- lows from the hypothesis. A prediction is what is expected to hap- pen if each hypothesis were true. For example, if hypothesis (a) is true, (owls hunt by keen night vision) then one can predict that the owl will pounce only on the mouse in either a light or a dark room. If hypothesis (b) is true (owls hunt by hearing), then one can pre- dict that in a lighted room, the owl will pounce closer to the mouse’s head. But, in a dark room, the owl should pounce closer to a rustling leaf attached to the mouse. Finally, if hypothesis (c) is true (owls hunt by sensing body heat), then an owl would strike only the prey no matter the room conditions, because owls hunt by detecting the prey’s body heat. 3 1 2 Copyright © by Holt, Rinehart and Winston. All rights reserved. A scientific study includes observations, questions, hypotheses, predictions, experiments, data analysis, and conclu- sions. A biologist can use the scientific method to set up an experiment to learn how an owl captures prey at night. FIGURE 1-9 1 OBSERVATION Owls capture prey on dark nights. 2 QUESTION How do owls detect prey on dark nights? 3 HYPOTHESES a) Owls hunt in the dark by vision. b) Owls hunt in the dark by hearing. c) Owls hunt in the dark by sensing body heat. THE SCIENCE OF LIFE 15 Notice that these predictions make it difficult to distinguish be- tween the vision and body heat hypotheses. The reason is that both hypotheses predict that the owl could grab the mouse in a dark room. Also, these three hypotheses do not eliminate all other factors that could influence how the owl finds its prey. However, testing predictions can allow one to begin rejecting hypotheses and thus to get closer to determining the answer(s) to a question. DESIGNING AN EXPERIMENT Biologists often test hypotheses by setting up an experiment. Step in Figure 1-9 outlines an experiment to test the hypotheses about how an owl hunts at night. First, experimenters set up a room with an owl perch high on one side and a small trap door on the other side for releasing mice. Then, they tied a leaf to each mouse’s tail with a string and released each mouse into the room. Next, each mouse ran silently across the room, but the leaf trailed behind, making a rustling noise. During half of the trials, the lights were on. During the other half, the room was dark. Technicians videotaped all the action in the chamber with an infrared light, which owls cannot see. The researchers then viewed the videos and measured the position of the owl’s strike relative to each mouse’s head. Performing the Experiment Many scientists use a controlled experiment to test their hypotheses. A controlled experiment compares an experimental group and a control group and only has one variable. The control group pro- vides a normal standard against which the biologist can compare results of the experimental group. The experimental group is iden- tical to the control group except for one factor, the independent variable. The experimenter manipulates the independent variable, sometimes called the manipulated variable. 4 4 EXPERIMENT 5 DATA COLLECTION AND ANALYSIS Measure and compare the distance from the owl’s strike to the mouse and to the leaf in light and dark. 6 CONCLUSION Data supported the hearing hypothesis: Owls hunt in the dark by hearing. prey Test predictions of the three hypotheses. Control: In the light Experimental: In the dark 1 2 3 4 5 6 7 8 9 10 11 Predicting Results Materials 2 Petri dishes with agar, cellophane tape, wax pen Procedure 1. Open one of the Petri dishes, and streak your finger across the surface of the agar. 2. Replace the lid, and seal it with the tape. Label this Petri dish with your name and a number 1. 3. Seal the second Petri dish with- out removing the lid. Label this Petri dish with your name and the number 2. 4. Write a prediction about what will happen in each dish. Store your dishes as your teacher directs. Record your observations. Follow your teacher’s directions for disposal of your dishes. Analysis Was your prediction accurate? What evidence can you cite to support your prediction? If you did not obtain the results you predicted, would you change your testing method or your prediction? Explain. Evaluate the importance of obtaining a result that does not support your prediction. Quick Lab mb06se_bios03.qxd 5/18/07 10:40 AM Page 15 16 CHAPTER 1 The independent variable in the owl experiment is the presence or absence of light. In the owl experiment, the control group hunts in the light, and the experimental group hunts in the dark. In addi- tion to varying the independent variable, a scientist observes or measures another factor called the dependent variable, or respond- ing variable, because it is affected by the independent variable. In the owl experiment, the dependent variable is distance from the owl’s strike to the mouse’s head. Testing the Experiment Some controlled experiments are conducted “blind.” In other words, the biologist who scores the results is unaware of whether a given subject is part of the experimental or control group. This factor helps eliminate experimenter bias. Experiments should also be repeated, because living systems are variable. Moreover, scien- tists must collect enough data to find meaningful results. COLLECTING AND ANALYZING DATA Most experiments measure a variable—the dependent variable. This measurement provides quantitative data, data measured in numbers. For example, in the experiment above, scientists mea- sured the distance of an owl’s strike from the prey’s head in cen- timeters, as shown in step of Figure 1-9. An event’s duration in milliseconds is also an example of quantitative data. Biologists usually score the results of an experiment by using one of their senses. They might see or hear the results of an experiment. Scientists also extend their senses with a micro- scope for tiny objects or a microphone for soft sounds. In the owl experiment, biologists extended their vision with infrared cameras. Analyzing and Comparing Data After collecting data from a field study or an experiment and then organizing it, biologists then analyze the data. In analyzing data, the goal is to determine whether the data are reliable, and whether they support or fail to support the predictions of the hypothesis. To do so, scientists may use statistics to help determine relation- ships between the variables involved. They can then compare their data with other data that were obtained in other similar studies. It is also important at this time to determine possible sources of error in the experiment just per- formed. Scientists usually display their data in tables or graphs when analyzing it. For the owl study, biologists could have made a bar graph such as the one in Figure 1-10, which shows the average distance from the owl’s strike relative to the mouse’s head or the leaf in the light and in the dark. 5 5 0 10 15 20 25 In the light In the dark Average distance from strike (cm) Distance Between Owl Strike and a Mouse or From a Leaf Attached to Mouse 30 Mouse Leaf Mouse Leaf The data below are hypothetical results that might occur from the described owl experiment.The independent variable is the darkness of the room, and the dependent variable is how far the owl struck from the mouse’s head.The data show that the owl strikes more accurately at the mouse in the light but strikes more accurately at the leaf in the dark. FIGURE 1-10 Copyright © by Holt, Rinehart and Winston. All rights reserved. THE SCIENCE OF LIFE 17 DRAWING CONCLUSIONS Biologists analyze their tables, graphs, and charts to draw conclu- sions about whether or not a hypothesis is supported, as shown in step of Figure 1-9. The hypothetical owl data show that in the light, owls struck with greater accuracy at the mouse than at the leaf, but in the dark, owls struck with greater accuracy at the leaf than the mouse. Thus, the findings support the hearing hypothe- sis, but not the vision hypothesis. An experiment can only disprove, not prove, a hypothesis. For example, one cannot conclude from the results that the hearing hypothesis is proven to be true. Perhaps the owl uses an unknown smell to strike at the mouse. One can only reject the vision hypothe- sis because it did not predict the results of the experiment correctly. Acceptance of a hypothesis is always tentative in science. The scientific community revises its understanding of phenomena, based on new data. Having ruled out one hypothesis, a biologist will devise more tests to try to rule out any remaining hypotheses. Making Inferences Scientists often draw inferences from data gathered during a field study or experiment. An inference (IN-fuhr-uhns) is a conclusion made on the basis of facts and previous knowledge rather than on direct observations. Unlike a hypothesis, an inference is not directly testable. In the owl study, it is inferred that the owl detects prey from a distance rather than by direct touch. Applying Results and Building Models As shown in Figure 1-11, scientists often apply their findings to solve practical problems. They also build models to represent or describe things. For example in 1953, James Watson and Francis Crick used cardboard balls and wire bars to build physical models of atoms in an attempt to understand the structure of DNA. Mathematical models are sets of equations that describe how dif- ferent measurable items interact in a system. The experimenter can adjust variables to better model the real-world data. CONSTRUCTING A THEORY When a set of related hypotheses is confirmed to be true many times, and it can explain a great amount of data, scientists often reclassify it as a theory. Some examples include the quantum the- ory, the cell theory, or the theory of evolution. People commonly use the word “theory” in a different way than scientists use the word. People may say “It’s just a theory” suggesting that an idea is untested, but scientists view a theory as a highly tested, generally accepted principle that explains a vast number of observations and experimental data. 6 Copyright © by Holt, Rinehart and Winston. All rights reserved. Biologists often apply their knowledge of the natural world to practical problems. Studies on the owl’s keen ability to locate sounds in space despite background noise are helping biotechnologists and bioengineers develop better solutions for people with impaired hearing, such as the people shown in this picture. FIGURE 1-11 18 CHAPTER 1 COMMUNICATING IDEAS An essential aspect of scientific research is scientists working together. Scientists often work together in research teams or sim- ply share research results with other scientists. This is done by publishing findings in scientific journals or presenting them at sci- entific meetings, as shown in Figure 1-12. Sharing information allows others working independently to verify findings or to con- tinue work on established results. For example, Roger Payne pub- lished the results of his owl experiments in a journal in 1971. Then, other biologists could repeat it for verification or use it to study the mechanisms introduced by the paper. With the growing impor- tance of science in solving societal issues, it is becoming increas- ingly vital for scientists to be able to communicate with the public at large. Publishing a Paper Scientists submit research papers to scientific journals for publica- tion. A typical research paper has four sections. First, the Introduction poses the problem and hypotheses to be investigated. Next, the Materials and Methods describe how researchers proceeded with the experiment. Third, the Results state the findings the experiment presented, and finally, the Discussion gives the significance of the experiment and future directions the scientists will take. Job Description Forensic biolo- gists are scientists who study biological materials to investigate potential crimes and other legal issues against humans and animals. Forensic scientists have knowledge in areas of biology, such as DNA and blood pattern analysis, and work in private sector and public laboratories. Focus On a Forensic Biologist As a law enforcement forensic specialist for the Texas Parks and Wildlife Department, Beverly Villarreal assists the game warden in investigations of fish and wildlife violations, such as illegal hunting and fishing. Villarreal analyzes blood and tissue samples to identify species of animals such as fish, birds, and reptiles. Her work helps game wardens as they enforce state laws regarding hunting and fishing. Most people think of forensic scientists as the glamorous crime investigators on TV, but according to Villarreal real forensic scientists “spend a great deal of time at a lab bench running analysis after analysis.” Many of the methods used in animal forensics, such as DNA sequenc- ing, are also used in human forensics. Education and Skills • High school—three years of science courses and four years of math courses. • College—bachelor of science in biol- ogy, including course work in zoology and genetics, plus experience in per- forming DNA analyses. • Skills—patience, attention to detail, and ability to use fine tools. Careers in BIOLOGY Forensic Biologist For more about careers, visit go.hrw.com and type in the keyword HM6 Careers. www.scilinks.org Topic: Scientific Investigations Keyword: HM61358 mb06se_bios03.qxd 5/18/07 10:40 AM Page 18 THE SCIENCE OF LIFE 19 1. What two principles make the scientific method a unique process? 2. Define the roles of observations and hypotheses in science. 3. Summarize the parts of a controlled experiment. 4. Summarize how we make conclusions about the results of an experiment. 5. Why is the phrase, “it’s just a theory” misleading? 6. Give another example of a conflict of interest. CRITICAL THINKING 7. Making Hypotheses On a nocturnal owl’s skull, one ear points up, and the other ear points down. Suggest a hypothesis for this observation. 8. Designing Experiments Design an experiment to establish if owls hunt by keen sight or hunt by heat seeking. 9. Calculating Information What was the average distance between the owl’s strike and the mouse if the recorded differences in this experiment were 25, 22, 19, 19, and 15? SECTION 3 REVIEW After scientists submit their papers to a scientific journal, the editors of that journal will send the paper out for peer review. In a peer review, scientists who are experts in the field anonymously read and critique that research paper. They determine if a paper pro- vides enough information so that the experiment can be duplicated and if the author used good experimental controls and reached an accurate conclusion. They also check if the paper is written clearly enough for broad understanding. Careful analysis of each other’s research by fellow scientists is essential to making scientific progress and preventing scientific dishonesty. HONESTY AND BIAS The scientific community depends on both honesty and good sci- ence. While designing new studies, experimenters must be very careful to prevent previous ideas and biases from tainting both the experimental process and the conclusions. Scientists have to keep in mind that they are always trying to disprove their favorite ideas. Scientists repeat experiments to verify previous findings. This allows for science to have a method for self-correction and it also keeps researchers honest and credible to their peers in the field. Conflict of Interest For most scientists, maintaining a good reputation for collecting and presenting valid data is more important than temporary prestige or income. So, scientists try to avoid any potential conflicts of interest. For example, a scientist who owns a biotechnology company and manufactures a drug would not be the best researcher to critically test that drug’s safety and effectiveness. To avoid this potential con- flict of interest, the scientist allows an unaffected party, such as a research group, to test the drug’s effectiveness. The threat of a potential scandal based on misleading data or conclusions is a pow- erful force in science that helps keep scientists honest and fair. Scientists present their experiments in various forms. The scientists above are presenting their work in the form of a poster at a scientific meeting. FIGURE 1-12 Copyright © by Holt, Rinehart and Winston. All rights reserved. The Internet can provide a wealth of scientific information for a report, but the information may not always be credible or accurate. You can use the methods above to check the accuracy and credibility of your sources. SCIENCE TECHNOLOGY SOCIETY SCIENCE ON THE INTERNET: A New Information Age I n the past, students research- ing a science topic would typ- ically begin their research by visiting a library to use printed reference materials, such as encyclopedias. Today, most stu- dents research topics by using a computer and searching for information on the Internet. The Internet can provide students with a wealth of infor- mation. But which Web sites have accurate information, and which Web sites do not? Checking Web Addresses Students should use the Web address, or URL, to establish the Web site’s credibility. Usually, the domain name can suggest who has published the Web site. Web sites can be pub- lished by governmental agen- cies (ends in “dot gov” or .gov), by educational institutions (ends in “dot edu” or .edu), by organizations (ends in “dot org” or .org), or by commercial businesses (ends in “dot com” or .com). Government Web sites are usually reliable. Examples of credible governmental Web sites are the National Institutes of Health (NIH) and the Food and Drug Administration (FDA). University and medical school sites are also reliable sources of information. Many organiza- tions that research and teach the public about specific diseases and conditions can also provide reliable information. Examples of such organizations are the American Cancer Society and the American Heart Association. Evaluating Web Sites The credibility of the author of the Web site should also be checked. Make sure the author is not trying to sell anything and is established in his or her field. For example, a health Web site’s author should be a med- ical professional. It is also important to check the date that the information was posted on the Web to ensure that the information is current. Also, the Web site should provide ref- erences from valid sources, such as scientific journals or govern- ment publications. Finally, the student should always double-check informa- tion between several reliable Web sites. If two or three reliable sites provide the same informa- tion, the student can feel confi- dent in using that information. Web Sites for Students The Internet Connect boxes in this textbook have all been reviewed by professionals at the National Science Teachers Association (NSTA). Students can trust that these sites are reliable sources for science- or health-related topics. REVIEW 1. Which types of Web addresses are the most reliable? 2. List four important features to evaluate when using a Web site for research. 3. Supporting Reasoned Opinions Why do you think a Web site that is advertising a product may not offer accurate information? REVIEW 20 www.scilinks.org Topic: Using the Internet Keyword: HM61589 mb06se_biosts.qxd 5/18/07 10:42 AM Page 20 TOOLS AND TECHNIQUES With proper equipment and good methods, biologists can see, manipulate, and understand the natural world in new ways. Microscopes are one of many useful tools used to unlock nature’s biological secrets. MICROSCOPES AS TOOLS Tools are objects used to improve the performance of a task. Microscopes are tools that extend human vision by making enlarged images of objects. Biologists use microscopes to study organisms, cells, cell parts, and molecules. Microscopes reveal details that otherwise might be difficult or impossible to see. Light Microscopes To see small organisms and cells, biologists typically use a light microscope, such as the one shown in Figure 1-13. A compound light microscope is a microscope that shines light through a spec- imen and has two lenses to magnify an image. To use this micro- scope, one first mounts the specimen to be viewed on a glass slide. The specimen must be thin enough for light to pass through it. For tiny pond organisms, such as the single-celled paramecium, light passing through the organism is not a problem. For thick objects, such as plant stems, biologists must cut thin slices for viewing. There are four major parts of a compound light microscope. For further description of the parts of a micro- scope, see the Appendix. 1. Eyepiece The eyepiece (ocular (AHK-yoo-luhr) lens) magnifies the image, usually 10 times. 2. Objective Lens Light passes through the specimen and then through the objective lens, which is located directly above the specimen. The objective lens enlarges the image of the specimen. Scientists sometimes use stains to make the image easier to see. 3. Stage The stage is a platform that supports a slide holding the specimen. The slide is placed over the opening in the stage of the microscope. 4. Light Source The light source is a light bulb that provides light for viewing the image. It can be either light reflected with a mirror or an incandescent light from a small lamp. SECTION 4 OBJECTIVES ● List the function of each of the major parts of a compound light microscope. ● Compare two kinds of electron microscopes. ● Describe the importance of having the SI system of measurement. ● State some examples of good laboratory practice. VOCABULARY compound light microscope eyepiece (ocular lens) objective lens stage light source magnification nosepiece resolution scanning electron microscope transmission electron microscope metric system base unit Compound light microscopes open the human eye to an interesting world including tiny pond organisms, healthy and diseased cells, and the functioning of cell parts. FIGURE 1-13 Objective lens Eyepiece (ocular lens) Stage Light THE SCIENCE OF LIFE 21 Copyright © by Holt, Rinehart and Winston. All rights reserved. 22 CHAPTER 1 Magnification and Resolution Microscopes vary in powers of magnification and resolution. Magnification is the increase of an object’s apparent size. Revolving the nosepiece, the structure that holds the set of objective lens, rotates these lenses into place above the specimen. In a typical com- pound light microscope, the most powerful objective lens produces an image up to 100 times (100) the specimen’s actual size. The degree of enlargement is called the power of magnification of the lens. The standard ocular lens magnifies a specimen 10 times (10). To compute the power of magnification of a microscope, the power of magnification of the strongest objective lens (in this case, 100) is multiplied by the power of magnification of the ocular lens (10). The result is a total power of magnification of 1000. Resolution (REZ-uh-LOO-shuhn) is the power to show details clearly in an image. The physical properties of light limit the ability of light microscopes to resolve images, as shown in Figure 1-14a. At pow- ers of magnification beyond about 2,000, the image of the speci- men becomes fuzzy. For this reason, scientists use other microscopes to view very small cellsLo sai che cos'è il fast fashion con fast fashion? Si intende quel settore dell'abbigliamento che realizza abiti a prezzi super ridotti e che lancia nuove collezioni di continuo pensate proprio per essere usate poco, il tutto sembra figo, no? Vestiti nuovi ogni volta che vuoi. Non è figo, ogni anno nel mondo vengono prodotti oltre 80 miliardi di capi d'abbigliamento e sulla terra siamo 8 miliardi e dopo il brevissimo periodo in cui vengono utilizzati tre capi su quattro finiscono in discarica o vengono inceneriti e soltanto un quarto viene riciclato Si stima che in un anno una persona compri circa 15 kg di vestiti. Eppure la sensazione è quella di non aver mai in mente da mettere e questo è esattamente quello che l'industria del fast fashion vuole. Lo sai che per produrre una t-shirt ci vogliono circa 3.900 litri di acqua l'equivalente di quello che beve una persona in cinque anni, un capo d'abbigliamento ha un impatto sull'ambiente in ogni fase della sua produzione, dalla produzione delle fibre, all'assemblaggio dal trasporto allo smaltimento, ma come è possibile che un top un prodotto che è stato coltivato come fibra trasformato in filato cucito dall'altra parte del mondo tinto confezionare e spedito costi meno di un panino? La risposta è semplice materie prime scadenti a basso costo abbinate quasi sempre allo sfruttamento dei lavoratori, la maggior parte dei capi di abbigliamento fast fashion viene prodotta in paesi come bangladesh, vietnam cambogia, spesso le condizioni di lavoro in questi paesi sono terribili e i diritti umani vengono calpestati, se paghiamo un top 7,95 significa che qualcun altro ha pagato il prezzo al posto nostro. Riassumendo il fast fashion nè non è sostenibile e probabilmente non ci rende più felici, ma l'abbigliamento è anche un modo per esprimere la propria personalità e creatività quindi ecco alcuni consigli. 1 comprare meno e curare meglio certo spendere tanto per una maglietta ci sembra assurdo ma ricordiamoci che una t-shirt a 4 euro probabilmente durerà poco o niente e soprattutto siamo sicuri di averne bisogno di 10? 2 scegliere bene i marchi alcuni siti possono aiutarti a scoprire nuovi brand etici e sostenibili e magari anche nuovi stili 3 riutilizzare e riparare, scambiamo i vestiti che non usiamo più quelle amiche quegli amici oppure vendiamoli sui mercatini online, ma soprattutto non buttiamoli appena salta un bottone, proviamo piuttosto a ripararli Come ultimo consiglio resiste l'impulso da shopping compulsivo, la maggior parte degli acquisti, soprattutto online in periodo di saldi vengono fatti d'impulso, fermati un momento e pensa a tutto ciò che quel vestito rappresenta, come è stato fatto, chi lo ha creato quanto ha inquinato e chiediti se ti serve davvero e ora che sai riconoscerlo cosa ne pensi del fast fashion?Il prezzo è l'espressione monetaria del valore, dal punto di vista del cliente, il prezzo che egli è disposto a pagare misura l'intensità del bisogno, nonché la quantità e la natura delle soddisfazioni che si aspetta; quanto al venditore, il prezzo al quale è disposto a vendere misura il valore dei fattori che compongono il prodotto, a cui si aggiunge il profitto che spera di realizzare. Definizione del prezzo da parte del mercato Il prezzo monetario può essere definito come un rapporto che indica l'ammontare di moneta necessaria per acquistare una quantità data di beni o servizi: prezzo = quantità di denaro ceduta dal cliente / quantità di beni ceduta dal venditore Il prezzo come misura del valore Per il cliente un prodotto rappresenta un paniere di attributi e i benefici che derivano dalla funzione base del prodotto e dall'insieme dei servizi supplementari, oggettivi e percepiti, che caratterizzano il prodotto o la marca → Il prezzo deve essere fissato in funzione del valore totale o dell'utilità globale percepita dal cliente, l'obiettivo del prezzo non è coprire i costi, ma catturare il valore percepito del prodotto nella mente del cliente. Il costo totale di acquisizione di un prodotto La quantità acquistata del bene misura solo parzialmente la quantità di soddisfazione ricevuta e la quantità di denaro ceduta misura solo in parte l'entità del sacrificio sostenuto. Il prezzo è il denaro che il venditore riceve al termine della transazione, ma non riflette per intero i costi a carico del consumatore; fra questi rientrano non solo il prezzo pagato, ma anche i termini di scambio (modalità pratiche che presiedono al trasferimento del titolo di proprietà) come: i termini di pagamento, i modi e i tempi di consegna, il servizio post-vendita ecc. Ecco alcune tra le principali fonti degli eventuali costi di trasferimento: costi di modifica del prodotti esistenti; cambiamenti nelle abitudini di consumo o di utilizzo del prodotto; spese di formazione o di riconversione degli utenti, investimenti per acquistare le nuove attrezzature necessarie all'utilizzo dei nuovi prodotti; costi di riorganizzazione e costi psicologici di cambiamento. Questi costi possono essere più elevati per alcuni clienti e meno per altri, rendendo il costo reale sostenuto dal cliente più elevato del prezzo monetario di vendita del prodotto; dal punto di vista del cliente, la nozione di prezzo comprende tutto l'insieme dei vantaggi offerti dal prodotto, nonché l'insieme dei sacrifici sostenuti dal cliente. Nell'ottica del cliente, il prezzo si definisce: prezzo = costo totale (monetario e non) a carico del cliente /vantaggi totali (tangibili e intangibili) forniti dal prodotto L'importanza delle decisioni di prezzo 1. Il prezzo influenza direttamente Il livello della domanda e determina il livello di attività: un prezzo elevato o troppo basso può compromettere lo sviluppo della domanda del prodotto; la misurazione della sensibilità al prezzo è un dato essenziale. 2.Il prezzo di vendita determina direttamente la redditivita dell'attività, determina: il margine di profitto, le quantità vendute, e stabilisce le condizioni di ammortamento degli investimenti nell'arco temporale stabilito. 3.Il prezzo di vendita stalbilito influenza la percezione globale del prodotto o marca e contribuisce al posizionamento della marca tra quelle note ai potenziali clienti; Il prezzo viene percepito come un segnale e si collega a un'idea di qualità e concorre quindi a creare l'immagine di marca. 4.il prezzo si presta più facilmente delle altre variabili di marketing al confronto tra prodotti o marche concorrenti; ogni minima variazione può stravolgere l’equilibrio di forze preesistenti. 5. la politica di prezzo deve essere compatibile con le altre componenti del marketing mix: Il prezzo deve consentire di finanziare le scelte pubblicitarie e promozionali; a un posizionamento di alta qualità e prezzo elevato deve corrispondere un packaging adeguato; la politica di prezzo deve rispettare le scelte distributive e consentire di raggiungere i margini di distribuzione necessari a centrare gli obiettivi di copertura del mercato. L'evoluzione dell'ambiente economico e competitivo ha contribuito ad accrescere l'importanza e la complessità delle decisioni di prezzo: ➥ l'accelerazione del progresso tecnologico e l'accorciamento del ciclo di vita dei prodotti implicano che un'attività nuova debba diventare redditizia in un intervallo di tempo più breve rispetto al passato. Un errore di fissazione del prezzo d'introduzione è più grave, in quanto più difficile da correggere. ➥ la proliferazione di marche e prodotti poco differenziati, il continuo emergere di nuovi prodotti e l'estensione delle linee di prodotti accrescono l'importanza di un posizionamento corretto in termini di prezzo, piccole differenze possono modificare in misura considerevole la percezione di una marca da parte del mercato. ➥ i vincoli legali, normativi e sociali che limitano l'autonomía dell'impresa nell'ambito della decisione dei prezzi. (fissazione di un tetto sui margini e l'obbligo di autorizzazione degli aumenti tariffari) ➥ i consumatori sono più attenti ai prezzi, soprattutto Il segmento dei millennial e della gen Z, tendono a confrontare immediatamente i prezzi, utilizzando le nuove tecnologie. Gli obiettivi delle decisioni di prezzo Tutte le imprese perseguono l'obiettivo di rendere redditizia la propria attività e di generare un surplus economico il più possibile elevato, gli obiettivi possibili sono classificabili in 3 categorie: 1. Gli obiettivi orientati al profitto → rientrano la massimizzazione del profitto e la realizzazione di un livello di redditività sufficiente sul capitale investito. L'obiettivo di massimizzare il profitto è il modello suggerito dagli economisti, nella pratica è di difficile applicazione, perché richiede conoscenze precise sulle funzioni di costo e domanda e perché presuppone una stabilità del fattori ambientali e competitivi che raramente si verifica nella realtà. L'obiettivo del tasso di redditività degli investimenti (ROI) cosiddetto "sufficiente" si traduce in pratica nel calcolare un prezzo target o un prezzo sufficiente, cioè un prezzo che per un previsto livello di attività, assicuri un ritorno "ragionevole" sul capitale investito. 2. Gli obiettivi orientati al volume → mirano a massimizzare il volume d'affari o la quota di mercato o ad assicurare un tasso di crescita sufficiente delle vendite. Massimizzare la quota di mercato comporta l'adozione di un prezzo di penetrazione, quindi basso ed inferiore a quello della concorrenza,per incrementare il volume delle vendite e la quota di mercato. Una volta raggiunta la posizione di leadership, l'obiettivo diventa quello di un tasso di redditività sufficiente o "soddisfacente", viene deciso quando le imprese che hanno accumulato un grande volume di produzione e prevedono pertanto una diminuzione dei loro costi. Attuare un prezzo di scrematura significa approfittare del fatto che certi gruppi di clienti sono disposti a pagare un prezzo elevato per l'alto valore distintivo (reale o percepito) del prodotto, l'obiettivo è realizzare un volume d'affari consistente attraverso una politica di prezzo elevato anziché di volume. 3. Gli obiettivi orientati alla concorrenza → mirano alla stabilizzazione del prezzi o all'allineamento con i prezzi dei concorrenti. In certi settori dominati da un'impresa leader, l'obiettivo è quello di instaurare un rapporto stabile fra i prezzi dei diversi prodotti in competizione e di evitare forti fluttuazioni che potrebbero compromettere la fiducia dei clienti. L'obiettivo dell'allineamento viene perseguito quando l'impresa si rende conto di non poter esercitare alcuna influenza sul mercato, soprattutto se è presente un impresa leader e se i prodotti sono standardizzati, indirizzerà i suoi sforzi verso forme di concorrenza diverse dal prezzo, che prevalgono in questo tipo di mercato (no-price competition). 18.2 Metodi di determinazione del prezzo Nella determinazione del prezzo, si tratta di indíviduare la migliore combinazione prezzo-quantità, tenendo conto dei vincoli determinati dai costi e dal mercati, le imprese possono impiegare 3 metodi diversi: La determinazione del prezzo basata sui costi → approccio più naturale ed immediato, per una (presunta) maggiore facilità di misurazione dei costi rispetto agli altri fattori. Il costo rappresenta il limite inferiore del prezzo: il produttore sostiene dei costi per realizzare e commercializzare i prodotti, quindi dovrà determinare il prezzo in modo da recuperare i costi sostenuti. L'analisi del costo permette di identificare 4 tipi di prezzi basati sul costi: ➥ Il prezzo soglia o prezzo minimo, è il prezzo corrispondente ai costi variabili (C), detti anche out-of-pocket costs. Il prezzo soglia, detto anche "prezzo marginale", è il prezzo minimo al di sotto del quale l'impresa non può scendere. Un commerciante può decidere di vendere alcuni prodotti a un prezzo soglia sperando di attrarre clienti che acquistino anche altri prodotti sui quali ci sia un certo margine di profitto.Permette di recuperare il solo costo di sostituzione del prodotto, con un margine lordo nullo: prezzo soglia = costo unitario variabile ➥Il prezzo tecnico o BEP (Break-Even Price), è Il prezzo corrispondente al punto di pareggio, cioè il prezzo che copre i costi variabili e i costi fissi per un dato volume di vendite; quindi che garantisce il recupero del valore di sostituzione del prodotto, la copertura dei costi fissi (F). prezzo tecnico = C + F/E(Q) dove E(Q) indica le quantità di prodotto che ci si attende di produrre (e vendere) nell'ipotesi del livello di attività considerata. ➥Il prezzo target o prezzo sufficiente, comprende, oltre ai costi variabili e fissi, un vincolo di profitto, cioè un margine di profitto generalmente determinato considerando un "normale" tasso di redditività (r) sul capitale investito (K). Il calcolo del prezzo target fa riferimento a un determinato volume di attività: prezzo target = C + F/E(Q) + r x K/ E(Q) dove K indica il capitale investito e r il tasso di redditività considerato sufficiente o normale. ➥il prezzo di ricarico o mark-up price, si calcola aggiungendo un ricarico standard al prezzo tecnico, viene usato per la sua semplicità, ignora del tutto la domanda e la concorrenza: si otterrà il margine desiderato solo al raggiungimento del livello di vendite atteso. prezzo di carico = prezzo tecnico / 1 - margine atteso Il rischio di ragionamento circolare L'inconveniente di questi metodi è la mancata considerazione del rapporto prezzo-volume, essi si basano su un ragionamento circolare implicito: il volume determina i costi, che determinano il prezzo, che a sua volta determina il livello della domanda. Nella realtà non è detto che il prezzo target o di ricarico adottato generi realmente il volume di attività in base al quale è stato calcolato. Es. Se la domanda non raggiunge la produzione di unità programmata per mantenere la redditività prevista sarà necessario aumentare il prezzo del prodotto stabilito inizialmente. L'utilità dei prezzi basati sui costi I prezzi orientati ai costi costituiscono solo un punto di partenza nel processo di definizione dei prezzi di mercato: non possono essere l'unica base per la determinazione del prezzo, perché non considerano né la domanda, né il valore percepito del prodotto, né la concorrenza. Sono utili in quanto forniscono una risposta alle seguenti domande: Quale volume di vendite bisogna raggiungere per coprire totalmente i costi? A che quota di mercato corrisponde il volume d'affari relativo alla soglia di redditività? ecc… Le decisioni di riduzione dei prezzi Il ricorso a una riduzione di prezzo in un'ottica di stimolazione della domanda è opportuno solo quando la domanda primaria è espandibile, in caso contrario, se l'impresa diminuisce i suoi prezzi e se tutti i concorrenti reagiscono immediatamente allineandosi, diminuiranno i profitti di tutti e le rispettive quote di mercato resteranno identiche. Esistono delle situazioni che possono essere favorevoli a una diminuzione dei prezzi in un mercato in cui la domanda primaria non è espandibile, senza determinare reazioni immediate da parte dei concorrenti,può succedere: Quando i concorrenti presentano costi superiori e non possono ridurli senza intaccare la propria redditività, ciò comporta la perdita di una quota di mercato, salvo quando determinati elementi di differenziazione neutralizzano lo scarto di prezzo. quando le imprese devono confrontarsi con concorrenti di piccole dimensioni che diminuiscono i prezzi, le piccole imprese possono sfruttare una diminuzione di prezzo che rappresenta un investimento meno pesante rispetto alle imprese con una quota di mercato consistente → per tale ragione i grandi concorrenti possono scegliere di mantenere i propri prezzi e di reagire su un altro terreno, per esempio mediante la pubblicità (costo fisso) Un'impresa può scegliere di non adeguarsi a una riduzione di prezzo, soprattutto quando il valore percepito del suo prodotto è superiore a quello del concorrenti diretti, gli elementi di differenziazione, come l'immagine, l'estensione dei servizi e la relazione con i clienti, a proteggerla dagli effetti di una riduzione di prezzo. La valutazione del costo di una riduzione di prezzo La diminuzione del prezzo è spesso molto onerosa, specie per un'impresa nella quale l'incidenza dei costi variabili è elevata, in quanto l'incremento della quantità venduta necessaria per mantenere il margine deve essere tanto maggiore quanto più è rilevante la quota dei costi variabili, l'aumento delle vendite necessario a mantenere lo stesso livello di redditività sarà così determinato: incremento volume di vendita (%) = ( x / M°- x) x 100 dove x è la percentuale di variazione di prezzo espressa in decimali e considerata in valore assoluto, mentre M° rappresenta la percentuale di margine lordo sul prezzo di vendita,in decimali, prima della diminuzione di prezzo. Le decisioni del rialzo dei prezzi L'impresa che da il via al rialzo del prezzo deve accertarsi della volontà di fare altrettanto da parte dei concorrenti che dipende dalle condizioni del mercato nel momento in cui il rialzo viene applicato, in particolare quando la capacità produttiva è pienamente utilizzata e la domanda cresce. L'impresa ha interesse a valutare il margine di manovra di cui dispone prima di avviare tale iniziativa, in caso di rialzo, la riduzione di volume tollerabile, che lascia invariato il precedente profitto, si determina come: tasso di riduzione tollerabile delle vendite (%) = (x /M° + x) x 100 dove x rappresenta la percentuale prevista di aumento del prezzo espressa come decimale. 18.3 La determinazione del prezzo basata sulla domanda In un'impresa orientata al mercato, il punto di partenza del processo decisionale è rappresentato dunque dal prezzo accettabile da parte del mercato, che a sua volta determina il costo target. La determinazione del prezzo in base alla domanda avviene pertanto in una prospettiva in cui la sensibilità del cliente rispetto al prezzo occupa un ruolo centrale. Il concetto di elasticità della domanda L'elasticità misura in modo diretto la sensibilità dei clienti rispetto al prezzo e permette di calcolare le quantità che saranno richieste a diversi livelli di prezzo. Definizione di elasticità rispetto al prezzo ⇒ ossia la variazione percentuale della domanda di un prodotto espressa in quantità, determin ata da una variazione di prezzo dell'1%; vale a dire: ε =% di variazione della domanda / % di variazione del prezzo L'elasticità al prezzo assume quasi sempre valori negativi, poiché un aumento di prezzo determina generalmente una riduzione delle quantità venduta, mentre una diminuzione di prezzo comporta generalmente un incremento delle vendite. I fattori che determinano la sensibilità del prezzo Nagle e Holden hanno identificato 9 fattori esplicativi della sensibilità al prezzo da parte dell'acquirente: 1. L'effetto del valore unico → Il prodotto presenta una o più qualità distintive di valore per l’acquirente, tangibili o intangibili, che lo differenziano dal prodotti della concorrenza 2. L'effetto della notorietà del sostituti → le alternative che si presentano al cliente (considerando sia i prodotti sia le marche concorrenti) e la misura in cui i potenziali clienti sono informati dell'esistenza di questi prodotti sostitutivi. 3. L'effetto della difficoltà di confronto → il grado di difficoltà incontrato dai clienti nei raffronti tra le offerte di diversi fornitori,se è possibile determinare gli attributi di un prodotto osservandolo se è necessario acquistarlo o consumarlo per capire che cosa offre, magari il prodotto presenta complessità e l'intervento di specialisti per valutare gli attributi che lo differenziano… 4. L'effetto della spesa totale → Per Il cliente, quanto è significativa la spesa per l'acquisto del prodotto, in valore assoluto e come percentuale (prodotto di consumo) del suo reddito disponibile? 5. L'effetto del vantaggio finale → Quali benefici ricerca l'acquirente nel prodotto, quanto è sensibile al costo dei benefici ricercati? Quale quota del beneficio ricercato copre il prezzo del prodotto? 6. L'effetto del costo condiviso → Il cliente paga la totalità del prezzo del prodotto? In caso negativo, che quota del prezzo paga effettivamente il cliente? 7. L'effetto dell'investimento passato → Il prodotto è utilizzato a complemento di un prodotto principale già acquistato e in previsione di un uso futuro? Per quanto tempo i clienti sono legati a queste spese? 8. L'effetto del rapporto qualità-prezzo → avere un'immagine di prestigio è un attributo importante per questo tipo di prodotto? Il prodotto aumenta il suo valore quando il livello elevato del suo prezzo porta a escludere alcuni gruppi di clienti? La perdita potenziale del cliente sarebbe alta nel caso in cui la qualità del prodotto si rivelasse insufficiente? 9. L'effetto scorta → I clienti detengono scorte importanti del prodotto? Ritengono o meno temporaneo il livello attuale del prezzo? Sensibilità al prezzo del cliente Industriale Porter rileva come i clienti che non sono sensibili al prezzo presentino una o più delle seguenti caratteristiche: • Il prezzo del prodotto di cui si sta valutando l'elasticità rappresenta una minima parte del costo totale di produzione del cliente e/o del suo budget di approvvigionamento. • La perdita subita a causa di un difetto del prodotto è elevata rispetto al costo del prodotto stesso. • La performance del prodotto (o servizio) consente un notevole risparmio o un netto miglioramento dei risultati per il cliente. • Il cliente adotta una strategia di qualità elevata, a cui il prodotto contribuisce notevolmente. • Il cliente ricerca un prodotto molto specifico o realizzato su ordinazione. • Il cliente presenta un'ottima redditività e/o può far sostenere facilmente il costo del prodotto acquistato ai propri clienti. • Il cliente è male informato sul prodotto e/o non acquista in base a esigenze specifiche. • Le motivazioni del centro d'acquisto responsabile della decisione Il calcolo del prezzo ottimale basato sull’elasticità La teoria economica sostiene che il prezzo ottimale (che massimizza gli utili), è inversamente proporzionale all'elasticità della domanda di un prodotto. Se l'elasticità rispetto al prezzo è nota, Il prezzo ottimale si calcola: POttimale = C x (ε / ε + 1) Oppure prezzo ottimale = costo diretto unitario x ricarico (mark-up) dove: ricarico (mark-up) = elasticità al prezzo / (elasticità al prezzo + 1) Il prezzo ottimale si ottiene aumentando il costo variabile unitario (o costo marginale) per una percentuale che è funzione dell'elasticità al prezzo e non dipende dal costo. Il coefficiente di ricarico ottimale è più elevato quando l'elasticità al prezzo ha un valore assoluto basso (cioè vicino all'unità). Quanto più l'elasticità si avvicina all'unità, tanto più elevato sarà il prezzo accettato dal mercato. I metodi di misurazione dell'elasticità al prezzo Possono essere raggruppati in 4 categorie principali: La prima include il metodo del giudizio degli esperti, che consiste nel chiedere ai responsabili di marketing di formulare tre previsioni sulla curva di risposta al prezzi, cioè le vendite attese, nell'ordi- ne: al prezzo più basso; al prezzo più alto possibile; a un livello di prezzo intermedio. è abbastanza valida e affidabile e presenta costi bassi, si può applicare sia ai prodotti nuovi ed esistenti. La seconda comprende le indagini dirette e indirette presso i consumatori, Il metodo più usato è quello indiretto dell'analisi congiunta, le analisi indirette risultano più utili di quelle dirette. La terza include le sperimentazioni di prezzo, sul campo o in laboratorio, è abbastanza valida e molto affidabile ma presenta costi alti, si può applicare sia ai prodotti nuovi ed esistenti. La quarta racchiude le analisi di dati storici, ovvero gli studi econometrici realizzati su dati presentati in ordine cronologico o emersi dai panel, è molto valida ma poco affidabile, i costi variano in base alla disponibilità e accessibilità, si può applicare solo ai prodotti già esistenti. Utilità delle misure dell'elasticità al prezzo I valori dell'elasticità permettono di sapere come agire sui prezzi per stimolare la domanda e aumentare il volume d'affari. I confronti tra i valori di elasticità di marche concorrenti permettono di identificare quelle in grado di resistere meglio ad aumenti di prezzo, il che rivela il loro potere di mercato. Il potere di mercato è misurato dalla capacità dell'impresa di imporre un prezzo superiore a quello praticato nei suoi diritti concorrenti; minore è l'elasticità della domanda più bassa sarà la sensibilità della quota di mercato di fronte a un aumento del prezzo del prodotto; quindi L'impresa che detiene un potere di mercato presenta una domanda meno elastica rispetto a quella di un prodotto poco differenziato ed è in grado di far accettare un prezzo superiore al gruppo di clienti sensibili all'elemento di differenziazione. I confronti tra i valori di elasticità del prodotti appartenenti a una stessa categoria permettono invece di modulare i prezzi all'interno della categoria stessa. Le elasticità incrociate permettono di prevedere gli spostamenti della domanda da una marca all'altra. Limiti delle misurazioni dell'elasticità al prezzo Tale approccio ha visto poche applicazioni pratiche, la nozione di elasticità presenta un certo numero di difficoltà concettuali e operative che riducono la sua utilità pratica, come: - misura una relazione basata sul comportamento d'acquisto ed è misurabile solo a posteriori. - Il suo valore predittivo dipenderà dalla stabilità delle condizioni dell'osservazione; - il problema non è tanto sapere come adattare i prezzi alla sensibilità attuale ma piuttosto come intervenire su tale sensibilità per modificarla nel senso voluto dall'impresa. - l'elasticità misura l'impatto del prezzo sulla quantità acquistata, ma non misura l'effetto del prezzo sulla propensione a provare il prodotto, sull'acquisto ripetuto, sulla percentuale di esclusività ecc. - nella pratica è spesso difficile ottenere stime di elasticità rispetto al prezzo abbastanza stabili e affidabili da consentire di "calcolare" un prezzo ottimale di vendita su tale base. L'approccio basato sul valore percepito Stabilisce il prezzo partendo dalle percezioni del consumatore, è una diretta conseguenza del concetto di prodotto come paniere di attributi. Dal punto di vista del consumatore, un prodotto corrisponde al paniere di vantaggi che derivano dal suo utilizzo, un'impresa orientata al mercato deve essere il valore percepito dal cliente dei benefici e dei costi del prodotto a guidare la determinazione del prezzo; i clienti pesano benefici e costi di un prodotto e preferiscono quello che offre il miglior rapporto qualità-prezzo. Il valore percepito del prodotto → L'analista di mercato deve capire le percezioni dei consumatori misurate con un metodo ‘composito’ basato sugli studi di Fishbein. Il punteggio del valore percepito è calcolato sulla base di: si valuta il grado di presenza percepito degli attributi tangibili ed intangibili (oltre al prezzo) su una scala da 1 a 10 rispetto a ciascuna marca. si moltiplicano le valutazioni espresse sugli attributi per il loro peso e poi si sommano i punteggi ottenuti; I risultati totali poi vengono trasformati in indici in rapporto al concorrente diretto, la marca che otterrà un punteggio superiore disporrà quindi degli attributi ritenuti migliori e secondo questa teoria potrà applicare un prezzo massimo accettabile superiore a quello dei concorrenti, Il valore è percepito di una marca non rappresenta il prezzo effettivamente praticabile ma solo il prezzo massimo praticabile. Il prezzo massimo accettabile → risulta utile quando si tratta di determinare Il prezzo di prodotti industriali, qualora Il vantaggio principale per l'acquirente sta la riduzione del costi. Per valutare quanto il cliente sia disposto a pagare, la procedura prevede di identificare: • identificare gli usi del prodotto dal punto di vista dell'acquirente (antiruggine,smacchiatore ecc..) • analizzare i diversi vantaggi offerti dal prodotto; (previene la ruggine, riduce i tempi e gli sforzi) • analizzare i costi sostenuti dal cliente per l'acquisto e l'utilizzo del prodotto; (installazione) • analizzare i vantaggi-costi, fissare il prezzo massimo accettabile da parte del cliente. Il prezzo massimo che il cliente è disposto a pagare (MAP, Maximum Acceptable Price): vantaggi - costi diversi dal prezzo = MAP I vantaggi possono essere funzionali (il servizio di base), finanziari, operativi o personali. I costi diversi dal prezzo possono essere: costi di acquisizione, d'installazione, di rischio o di malfunzionamento, di modifica delle abitudini ecc. Il confronto tra il prezzo massimo accettabile e i prezzi del concorrente permette di valutare il margine di manovra di cui l'impresa dispone. 18.4 La determinazione del prezzo basata sulla concorrenza Il grado di autonomia dell'impresa sui prezzi è influenzato da 2 fattori: la situazione concorrenziale del settore di riferimento e l'importanza del valore percepito del prodotto da parte dei clienti. L’autonomia tenderà a diminuire all’aumentare del numero di concorrenti, il valore percepito del prodotto può dare un vantaggio rispetto alla concorrenza, ove esista un elemento di differenziazione, percepito come un valore da parte del cliente, quest'ultimo è disposto a pagare un prezzo superiore a quello del prodotto concorrente, monopolio o di oligopolio differenziato → numero dei concorrenti è basso e il valore percepito elevato, l’impresa ha ampia autonomia. concorrenza pura → numero di concorrenti è elevato e il valore percepito basso, sono la domanda e l'offerta a definire il livello del prezzo di mercato. L'impresa non ha alcuna autonomia sui prezzi. oligopolio indifferenziato → il numero di concorrenti e il valore percepito sono bassi, l'interdipendenza tra i concorrenti è alta e limita l'autonomia di ognuno, si applica una strategia di allineamento del prezzo in base a quello del produttore leader di mercato. concorrenza monopolistica o imperfetta →il numero di concorrenti è elevato ed il valore percepito elevato, c'è una certa autonomia ma limitata dall'intensità della concorrenza. Prevedere il comportamento dei concorrenti Nelle situazioni di oligopolio indifferenziato, in cui la domanda primaria non è più espandibile e i prodotti offerti dalle imprese concorrenti sono poco differenziati; l'impresa può allinearsi ai prezzi dei concorrenti o leader del settore; fissare il prezzo ad un livello superiore, con il rischio di perdere quote di mercato; oppure fissare il prezzo ad un livello inferiore con il rischio di una guerra dei prezzi. Il risultato di queste strategie dipende dalle reazioni dei concorrenti, l'obiettivo di un'analisi della concorrenza sui prezzi consiste nel valutare la capacità d'azione dell'impresa e l'elasticità nella reazione della concorrenza e, in particolare, nel calcolare le elasticità di reazione dei concorrenti più pericolosi in caso di aumento o diminuzione del prezzo. Una guerra dei prezzi può consentire ad alcune imprese di migliorare la propria posizione concorrenziale compensato da un aumento della quota di mercato, inoltre può portare all'eliminazione di un concorrente potenzialmente pericoloso. 18.5 La gestione del prezzo Le imprese non applicano un prezzo di vendita unico, ma una serie di prezzi, adatti a diverse situazioni di mercato. prezzi flessibili → quando uno stesso prodotto viene venduto a clienti diversi a prezzi diversi, trova spiegazione nelle differenze tra i clienti, che presentano una diversa sensibilità al prezzo, ma anche nelle differenze nei costi e negli obiettivi promozionali. Quando le variazioni adottate non sono giustificate da differenze nei costi, si parla di discriminazioni di prezzo. Esistono 5 modi per ottenere una flessibilità del prezzo: 1. Sconti nel mercati secondari → succede quando l'impresa ha un eccesso di capacità produttiva e ha l'opportunità di vendere in un mercato nuovo senza aumentare i propri costi fissi/variabili e senza correre il rischio di perdere vendite sul suo mercato principale. L'impresa non può adottare un prezzo inferiore a quello soglia. Queste strategie trovano applicazione nel commercio internazionale, con alcuni gruppi socio demografici (studenti, bambini, anziani). Bisogna assicurarsi che chi acquista a prezzo ridotto non possa rivendere i prodotti sul mercato principale a causa degli alti costi di transazione. 2. Lo sconto stagionale → si adottano prezzi diversi per un prodotto destinato a potenziali clienti con una sensibilità al prezzo diversa all'inizio e alla fine della stagione: chi vuole acquistare solo ad inizio stagione è poco sensibile al prezzo; altri sono disposti ad acquistare in qualsiasi momento, ma sono molto sensibili al prezzo. L'impresa venderà a un prezzo elevato all'inizio della stagione, per poi abbassarlo sistematicamente alla fine. (prodotti di moda venduti fuori stagione); le riduzioni stagionali di prezzo sono note e prevedibili da parte dei consumatori. 3. Sconti casuali → alcuni clienti sono disposti a impegnare più tempo per cercare l'offerta migliore, mentre altri no. L'obiettivo dell'azienda è vendere a un prezzo più alto ai clienti poco informati ed evitare che i consumatori informati acquistino a un prezzo più basso dalla concorrenza. Questa strategia richiede di mantenere il prezzo alto e di applicare lo sconto a intervalli casuali; non prevedibili, in modo che gli acquirenti non informati comprino a caso al prezzo più alto, e quelli informati aspettino l'arrivo dello sconto. 4. I prezzi promozionali → ridurre temporaneamente i prezzi per stimolare le vendite. I prezzi promozionali sono: i prezzi invito dei supermercati, le offerte speciali, i finanziamenti a basso tasso di interesse offerti dai concessionari, le offerte di rimborso, ecc. presentano il vantaggio, per il produttore, di essere temporanee e di consentirgli di tornare facilmente al prezzo di base. Negli ultimi decenni, si è assistito a un proliferare di promozioni, che hanno fatto perdere credibilità alla politica di prezzo delle marche e dei distributori, per riconquistarla sono state adottate 2 politiche tariffarie: quella dei prezzi "equi" EDFP (Every Day Fair Pricing), e quella dei "saldi quotidiani" EDLP (Every Day Low Pricing), ossia di prezzi leggermente ridotti disponibili sempre. Un tipo di prezzo promozionale popolare fra i produttori è l’offerta di rimborso, che permette di stimolare le vendite senza dover modificare il prezzo di base, sono buoni sconto da rispedire al fabbricante dopo l'acquisto, che danno diritto a un rimborso. I vantaggi sono: - la promozione non rischia di danneggiare l'immagine di marca. - si può offrire lo sconto direttamente al consumatore, svincolandosi dal distributore - Il produttore può interrompere la promozione quando lo desidera per mettere a punto l'inventario o rispondere ai concorrenti senza abbassare il prezzo. - ha un basso costo, perché molti consumatori dimenticano di rispedire il coupon per richiedere il rimborso a cui hanno diritto, permettendo così al produttore di offrire sconti "fantasma". - il coupon restituito da informazioni sui clienti utili per il marketing diretto, in quanto va compilato con nome, indirizzo e altri dati sul consumatore. 5. Gestione dei prezzi → adattamento dei prezzi di listino in base alle condizioni di realizzazione della vendita: quantitativi ordinati, tipo di intermediari, aree geografiche ecc.. Questi prezzi/sconti sono volti a ricompensare i clienti il cui comportamento d'acquisto permette all'impresa di risparmíare sui costi delle transazioni. es. riduzioni di prezzo sulla quantità, per pagamento in contanti ecc. Lo yield management e i prezzi dinamici La pratica della discriminazione dei prezzi è diffusa nell'ambito dei servizi, in particolare nei settori a capacità produttiva limitata e fissa, come l'industria alberghiera, le compagnie aeree ecc., settori che devono gestire i ricavi generati da attività deperibili e hanno in comune le seguenti caratteristiche: l'offerta è rappresentata da un servizio; il servizio può essere prenotato in anticipo; la capacità di produzione è fissa e presenta un costo di accrescimento molto elevato; la domanda è segmentabile in base a criteri di flessibilità e sensibilità al prezzo Il metodo dello Yield management consiste nel commercializzare prima i servizi a prezzo ridotto e poi quelli a prezzo pieno, permette di costruire una scaletta di prezzi; per esempio se prendiamo il caso di una compagnia aerea verranno prima venduti a basso prezzo i biglietti a chi acquista in largo anticipo ovvero è sensibile al prezzo, poi verranno riservati posti ad un prezzo più elevato es. per chi viaggia per lavoro ed è meno sensibile al prezzo. Con l'applicazione di prezzi dinamici le aziende stabiliscono prezzi flessibili per la propria offerta in base agli algoritmi che tengono conto anche dei prezzi e dell'offerta di concorrenti oltre che della domanda; Il prezzo non varia in base a variabili correlate al cliente ma variabili come l'ora del giorno, l'offerta disponibile, il volume di traffico nella pagina ecc.. La tariffazione dinamica è stata introdotta nell'industria dei trasporti aerei negli Stati Uniti negli anni 80 ed ora molti altri operatori adottano questo metodo, come gli hotel, autonoleggi, huber.. nel turismo il prezzo è basato sul tempo; prezzi più alti vengono addebitati durante l'alta stagione o durante eventi speciali mentre in bassa stagione addebitano a prezzi più bassi; l'obiettivo del prezzo dinamico in questo settore è trovare il pezzo più alto che i consumatori sono disposti a pagare La flessibilità dei prezzi online Il commercio online favorisce la relazione di tipo one-to-one, facilita quindi l'approccio della determinazione del prezzo su misura; esistono 5 condizioni che devono verificarsi indipendentemente dal fatto che il mercato sia online o offline; Affinché si possano applicare discriminazioni sui prezzi: 1) i clienti devono essere eterogenei nella loro sensibilità al prezzo: alcuni pronti a pagare molto, altri a scegliere il prezzo più basso disponibile sul mercato. 2) il mercato deve essere segmentabile. 3) le possibilità di arbitraggio devono essere limitate, i clienti che hanno acquistato a basso prezzo non devono essere in grado di rivendere il prodotto con profitto a un prezzo più alto. 4) il costo della segmentazione non deve superare il reddito derivato dalla personalizzazione della vendita. 5) la percezione di equità (fairness) della transazione non può essere violata, si intende la sensazione dell'acquirente che la transazione sia conveniente per entrambe le parti. I meccanismi di Individuazione dei prezzi su internet Si identificano 5 meccanismi di transazione principali: 1. Nell'offerta di prezzo standard, i prezzi sono predeterminati per uno specifico prodotto o servizio. 2. Le aste (eBay) sono un metodo in cui un individuo partecipa con le proprie offerte contro altri per comprare le merci da un terzo soggetto. 3. Le aste inverse (Magento.com), dette anche "richieste di quotazione" sono un metodo d'acquisto in cui un'organizzazione definisce il prezzo che è disposta a pagare e i fornitori partecipano con la propria offerta; 4. Gli scambi 5. Gli acquisti di gruppo, il fornitore offre un prodotto/servizio a un prezzo basso e scontato e la transazione si realizza se l'acquisto viene fatto da un numero minimo di persone stabilito in anticipo. La pratica della price leadership Un'impresa grazie alla propria dimensione o posizione, può occupare una posizione di leadership "naturale" del mercato; le sue decisioni sui prezzi sono riconosciute e accettate dalle altre imprese presenti sul mercato di riferimento. Esistono diversi tipi di leadership: ⭆ la leadership dell'impresa dominante è quella dell'impresa che detiene la quota di mercato maggiore e che stabilisce un prezzo e lascia che gli altri vendano la loro produzione a quel prezzo. Il leader deve essere potente e indiscusso e deve accettare di mantenere un prezzo elevato. ⭆la leadership barometrica consiste nell'avviare aumenti e diminuzioni di prezzo che si rivelano necessari, alla luce delle variazioni del costi di produzione e dell'andamento della domanda. ⭆la leadership tacita è quella in cui un'azienda è tacitamente riconosciuta come leader senza che vi sia intesa o accordo formale, cosa che sarebbe illegale. Per esercitare la leadership in modo efficace è necessaria la concomitanza di molti fattori: - disporre di un sistema informativo di mkt efficiente, che consenta di comprendere le evoluzioni del mercato e di reagire di conseguenza. - preoccuparsi realmente dello stato di salute del settore e utilizzare metodi per misurare la performance manageriale a lungo termine. - saper guidare il settore in modo responsabile e che agisca in modo da preservare, a breve termine, la stabilità delle quote nel mercato di appartenenza. - la presenza di un leader è un fattore di stabilità e riduce il rischio di una guerra dei prezzi. 18.6 I prezzi di una gamma di prodotti Le imprese hanno diverse gamme di prodotti e, all'interno di ogni gamma, alcuni prodotti sono sostituti potenziali e altri sono complementari, questa strategia ha determinato la comparsa di legami d'interdipendenza tra i prodotti che si traducono in un effetto di sostituzione (cannibalizzazione), o in un effetto di complementarità. Nella determinazione dei prezzi è necessario tener conto di questa interdipendenza. La nozione di elasticità incrociata Permette di misurare il grado d'interdipendenza fra i prodotti venduti con una stessa marca/impresa, e di osservare il tipo d'interdipendenza laddove presente: complementarietà o sostituibilità. Nel caso di due prodotti A e B, si definisce nel modo seguente: elasticità incrociata = % di variazione delle quantità venduta di A / % di variazione del prezzo di B Se l’elasticità incrociata è positiva, fra i prodotti sussiste un effetto di sostituzione; se è negativa vi è invece complementarietà, se è nulla o vicinissima allo zero, i prodotti si dicono indipendenti. La definizione del prezzo della gamma I prezzi collegati → nel caso di prodotti complementari o indipendenti (prodotti tra loro collegati ma non sostituibili gli uni agli altri), l'impresa può offrire prezzi collegati, per cui i prodotti possono essere acquistati separatamente oppure in blocco, a un prezzo sensibilmente inferiore alla somma dei prezzi individuali. es.mercato delle automobili in cui, al momento di acquistare una vettura, vengono offerte opzioni d'acquisto di assortimenti di prodotti collegati. Il premium price → si applica quando per uno stesso prodotto si offrono più versioni o modelli (un modello base o standard e un modello superiore), i clienti potenziali del modello base sono molto sensibili al prezzo, diversamente da quelli interessati al modello superiore. La soluzione sta nello sfruttare le economie di scala e l'eterogeneità della domanda, rispondendo alle esigenze dei segmenti con un prodotto di fascia bassa = prezzo contenuto e un prodotto di fascia alta = prezzo elevato. Prezzo e immagine → assegna il prezzo in base all'immagine del prodotto, l'obiettivo è segnalare agli acquirenti la qualità del prodotto e utilizzare il guadagno ottenuto dalla versione più costosa per abbassare il prezzo della versione economica, in questo caso, non esiste differenza tra i prodotti o le marche, se non nell'immagine e nel posizionamento percepito. I prezzi del prodotti complementari → fra i prodotti complementari abbiamo i rasoi e le lamette: le automobili e i pezzi di ricambio ecc.. quando i clienti sono fedeli alla marca e vogliono acquistare gli articoli/accessori originali, l'impresa può praticare prezzi contenuti per l'attrezzatura di base e un prezzo elevato per i prodotti complementari. 18.7 Il prezzo dei nuovi prodotti Più il nuovo prodotto è originale e apporta una soluzione innovativa, tanto più è sensibile al prezzo. Il prezzo di lancio è fondamentale e condiziona il successo commerciale e finanziario dell'operazione. L'impresa deve scegliere fra 2 strategie contrapposte: La strategia del prezzo di scrematura → consiste nel vendere il nuovo prodotto a un prezzo elevato, rivolgendosi all'estremità superiore della curva di domanda, in modo da garantire rapidamente rientri finanziari dopo il lancio. Considerazioni che vanno a sostegno di questa strategia: ⭆ Quando si ritiene che il ciclo di vita del nuovo prodotto sarà breve o che il prodotto verrà rapidamente imitato dalla concorrenza, ⭆ Quando la domanda è anelastica, l'impresa può sfruttare questo vantaggio adottando un prezzo elevato, per poi adeguarlo progressivamente quando il mercato entra in una fase di maturità. ⭆ è utile quando l'introduzione di un nuovo prodotto richiede investimenti in pubblicità e promozione e l'impresa non dispone della liquidità necessaria, applicare prezzi elevati costituisce una forma di finanziamento che permette di generare le risorse necessarie alla strategia di lancio. La strategia del prezzo di penetrazione → consiste nel praticare prezzi bassi per occupare una quota di mercato rilevante sin dall'inizio, presuppone di adottare un sistema di distribuzione intensivo attraverso azioni pubblicitarie e di predisporre un'adeguata capacità produttiva fin dal lancio del prodotto. Vi sono alcune condizioni generali che devono prevalere: ⭆ la domanda deve essere elastica al prezzo lungo tutta la curva. ⭆ non esiste un segmento da privilegiare e la strategia da adottare consiste nel rivolgersi alla totalità del mercato con un prezzo sufficientemente basso da adattarsi al maggior numero di clienti. ⭆ viene applicata per scoraggiare l'ingresso nel mercato di nuovi concorrenti perchè i prezzi bassi costituiscono una barriera all'entrata molto efficace, ⭆ la strategia del prezzo di penetrazione è più rischiosa della strategia di scrematura. The expression 2 + 4 1 + 2 is equal to (A) 0 (B) 1 (C) 2 (D) 4 (E) 5 2. The ones (units) digit of 542 is 2. When 542 is multiplied by 3, the ones (units) digit of the result is (A) 9 (B) 3 (C) 5 (D) 4 (E) 6 3. Some of the 1 × 1 squares in a 3 × 3 grid are shaded, as shown. What is the perimeter of the shaded region? (A) 10 (B) 14 (C) 8 (D) 18 (E) 20 4. If 3x + 4 = x + 2, the value of x is (A) 0 (B) −4 (C) −3 (D) −1 (E) −2 5. Which of the following is equal to 110% of 500? (A) 610 (B) 510 (C) 650 (D) 505 (E) 550 6. Eugene swam on Sunday, Monday and Tuesday. On Monday, he swam for 30 minutes. On Tuesday, he swam for 45 minutes. His average swim time over the three days was 34 minutes. For how many minutes did he swim on Sunday? (A) 20 (B) 25 (C) 27 (D) 32 (E) 37.5 7. For which of the following values of x is x 3 < x2 ? (A) x = 5 3 (B) x = 3 4 (C) x = 1 (D) x = 3 2 (E) x = 2112 years, Janice will be 8 times as old as she was 2 years ago. How old is Janice now? (A) 4 (B) 8 (C) 10 (D) 2 (E) 6 10. In the diagram, pentagon T P SRQ is constructed from equilateral 4 P T Q and square P QRS. The measure of ∠ST R is equal to (A) 10◦ (B) 15◦ (C) 20◦ (D) 30◦ (E) 45◦ Q P R S T Part B: Each correct answer is worth 6. 11. In the diagram, which of the following points is at a different distance from P than the rest of the points? (A) A (B) B (C) C (D) D (E) E y A x 2 2 4 4 6 8 6 8 B C D E P 12. If x = 2 and y = x 2 − 5 and z = y 2 − 5, then z equals (A) −6 (B) −8 (C) 4 (D) 76 (E) −4 13. In the diagram, P QR is a straight line segment. If x + y = 76, what is the value of x? (A) 28 (B) 30 (C) 35 (D) 36 (E) 38 x° x° x° y° y° P Q R 14. The line with equation y = 2x − 6 is reflected in the y-axis. What is the x-intercept of the resulting line? (A) −12 (B) 6 (C) −6 (D) −3 (E) 0 15. Amy bought and then sold 15n avocados, for some positive integer n. She made a profit of $100. (Her profit is the difference between the total amount that she earned by selling the avocados and the total amount that she spent in buying the avocados.) She paid $2 for every 3 avocados. She sold every 5 avocados for $4. What is the value of n? (A) 100 (B) 20 (C) 50 (D) 30 (E) 8 16. If 3x = 5, the value of 3x+2 is (A) 10 (B) 25 (C) 2187 (D) 14 (E) 458.E.1.2 VocabularyNC 8th Grade Science 8.E.1.2 Received: 26 November 2019 Revised: 10 January 2020 Accepted: 19 January 2020 DOI: 10.1111/obr.13005 PEDIATRICS/PHYSIOLOGY Adipokines: A gear shift in puberty Desirée Nieuwenhuis | Natàlia Pujol-Gualdo Amanda J. Kiliaan Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Center PRIME, Nijmegen, The Netherlands Correspondence Amanda J. Kiliaan, PhD, Associate Professor, Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Preclinical Imaging Center PRIME, Radboud university medical center, 6500 HB Nijmegen, Geert Grooteplein 21N 6525 EZ Nijmegen, The Netherlands. Email: amanda.kiliaan@radboudumc.nl Funding information Europees Fonds voor Regionale Ontwikkeling (EFRO), Grant/Award Number: BriteN 2016 1 | INTRODUCTION The prevalence of obesity in adolescents and children is increasing in | Ilse A.C. Arnoldussen | Summary In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed overview of the biological processes of two major players, leptin and adiponectin. Adipokines, especially leptin and adiponectin, seem to induce an early onset of puberty in girls and boys with obesity by affecting the hypothalamic-pituitary- gonadal (HPG) axis. Moreover, adipokines and their receptors are expressed in the gonads, suggesting a role in sexual maturation and reproduction. All in all, adipokines may be a clue in understanding mechanisms underlying the onset of puberty in child- hood obesity and puberty onset variability. KEYWORDS adipokines, obesity, puberty 1,2 the age of 5 years were overweight or were with obesity in 2016, and 3 Obesity is defined by an excessive accumulation of white adipose tissue (WAT), and it is often indicated by a body mass index (BMI) 4 above 30. Two main types of adipose tissue were described: WAT and brown adipose tissue (BAT), which differ in morphology and func- 5-7 Ilse A.C. Arnoldussen and Amanda J. Kiliaan contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation Obesity Reviews. 2020;21:e13005. wileyonlinelibrary.com/journal/obr 1 of 10 https://doi.org/10.1111/obr.13005 alarming rates. Specifically, worldwide, 41 million children below this number is expected to increase to 70 million in 2025. obesity is associated with various severe health complications, includ- ing increased risk of diabetes mellitus type 2, hypertension, heart dis- eases, and disturbances in sex hormone levels. 5,6 and mitochondria and plays a role in thermogenesis. Adipocytes in tion. BAT consists of adipocytes containing multiple lipid droplets WAT contain only a few mitochondria and a single lipid droplet. Adipose tissue has several functions including the storage of energy, thermogenesis, and the production and secretion of adipokines Generally, two physiological processes, adrenarche and gonadarche, 11,24 Childhood 5,7,8 a key role in puberty onset. Puberty is known as a period through which the body changes physically, being a physiological process resulting in the maturation of children, i.e. they develop sexual characteristics and obtain reproduc- 9,11 Adipokines are involved in a number of physiological processes including blood pressure, metabo- lism, glucose, and vascular homeostasis and may play amongst others 8-10 (hormones, cytokines, and peptides). tive functions. between obesity and puberty,2,12-23 the biological mechanisms under- lying obesity and puberty onset remain unclear. Hereafter, we review in detail the role of adipokines in the onset of puberty in childhood obesity. Although many studies have shown associations 2 | INITIATION OF PUBERTY PHYSIOLOGICAL PROCESSES IN THE interact to regulate the onset of puberty. During adrenarche, the adrenal cortex secretes steroid hormones (including 2 of 10 NIEUWENHUIS ET AL. androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and cortisol), insulin-like growth factor, and growth hormone, which contribute to the pubertal insights on new genetic loci (e.g. melanocortin-4 receptor, mitochon- drial carrier 2, and mitogen-activated protein kinase 13) and on sev- eral pathways that regulate the timing of puberty; however, it partly 34 9,24,25 Both adrenarche and gonadarche are involved in the development growth spurt, body odor, skin oiliness, and skeletal maturation. explains puberty timing variation. Thereby, defining the role of 25 adipokines is of importance in elucidating the variability in puberty as the expression of adipokines is sex-specific and is altered with body composition, adiposity, and during growth spurts. Moreover, adipokines and their receptors are expressed in gonads and several brain regions suggesting involvement in the onset of puberty and sex- ual maturation. Lastly, adipokines interfere in processes regulating timing and duration of puberty, for instance in the HPA and HPG axes which are both key players during adrenarche and gonadarche. Involvement of adipokines in the onset of puberty and specifically in individuals with obesity will be further reviewed in the next 2,24 3 | Puberty onset in girls is assessed using different markers, such as thelarche (breast development), menarche (the start of of pubic hair. pituitary-gonadal (HPG) axis is activated,2,26 and several hormones have been identified to participate in the activation of the HPG axis During gonadarche (Figure 1), the hypothalamic- 2,27 Kisspeptin, neurokinin B, and dynorphin are released by specialized including kisspeptin, neurokinin B, dynorphin, leptin, and ghrelin. 28 key regulator of the pulsatile secretion of gonadotropin releasing neurons, the KNDy neurons in the hypothalamus. Kisspeptin is a 29,30 B stimulates, and dynorphin inhibits the release of kisspeptin, which hormone (GnRH) from the hypothalamus. In addition, neurokinin implies that both coordinate a pulsatile release of kisspeptin. 31 Sub- sections. sequently, the activated HPG axis induces the pituitary gland to secrete luteinising hormone (LH) and follicle stimulating hormone (FSH). As a result, gametogenesis occurs, and the gonads will release sex hormones. Consequently, secondary sex characteristics develop including breast development in girls and an increased testicular vol- 2,26,32 is possibly due to differences in levels of body fat, hypothalamic-pitui- THE ONSET OF PUBERTY IN GIRLS ume in boys. The age at puberty onset varies greatly among individuals, which 19 35 menstruation), and pubic hair development. 33 genome-wide association studies have provided important new tary-adrenal (HPA) axis activity, and genetic background. Recent The average age of However, this age differs between cultures and ethnicities, and since 1980, age at menarche is girls at start of menarche is 12.4 years. 36 significantly decreasing. 36-39 F I G U R E 1 Hormonal regulation in the initiation of puberty in boys and girls. The secretion of kisspeptin, neurokinin B, and dynorphin from KNDy neurons initiate the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. This activates the pituitary gland to produce and secrete luteinising hormone (LH) and follicle stimulating hormone (FSH), which in turn stimulate the gonads to produce estrogen and testosterone in girls and boys, respectively 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 3 of 10 T A B L E 1 Summary of included studies Authors Year Country Study Design Primary Outcome Sex Sample Size (n) Age (y) Data Collection Lian et al21 2019 China Cross-sectional Puberty starts earlier in Chinese Han girls with obesity compared with Chinese Han girls with normal weight. Girls 2996 9-19 2012 and 2013 Biro et al12 Lazzeri et al20 2018 USA 2018 Italy Longitudinal Cross-sectional Body mass index had a greater effect on age at menarche than did race and ethnicity. Girls 946 6-16 2004-2014 Li et al23 2018 China Longitudinal For both, boys and girls, a higher BMI (ie, overweight and obese) is associated with earlier onset of puberty Girls Girls Boys Girls 542 Deng et al22 Flom et al15 2017 China Cross-sectional Increased BMI is associated with early timing spermarche and menarche. Boys Girls Girls 1278258 9-15 2005-2012 He et al24 Holmgren et al17 2017 China 2017 Sweden Cross-sectional Longitudinal Onset of puberty is not related to obesity in boys. Boys Boys Girls Girls 782 7-17 972 929 5839 Kelly et al19 2017 UK 2016 Brazil 2016 USA Longitudinal prospective cohort Higher BMI in girls is associated with the onset of menstruation at an earlier age. 11 10-18 11-17 Barcellos Gemelli et al25 Cross-sectional Longitudinal Excess weight is associated with early age of menarche. Girls 727 2014 2003-2009 Glass et al16 Lee et al26 In girls, but not in boys, greater adiposity is associated with the earlier onset of puberty. Boys Girls 135 Cabrera et al27 Leonibus et al14 2014 USA 2013 Italy Cross-sectional Longitudinal Thelarche occurred earlier than recently reported, while age of menarche remained unchanged. Girls 610 3-17.9 2007 2005-2012 Currie et al13 2012 Europe, USA, Canada Cross-sectional Overweight/obesity during childhood predicts the early onset of puberty in girls. Girls 20410 11, 13, 15 2005-2006 2017 USA Prospective birth cohort Overweight/obese status at the age of 7 ye was associated with increased risk of early menarche 788 From birth to menarche occurred Pregnancies 1959-1966 2016 USA Cross-sectional Boys with overweight enter puberty earlier compared with boys with normal weight or obesity, while puberty starts later in boys with obesity compared with boys with normal weight and overweight. Boys 3872 6-16 2005-2010 Overweight during childhood shows a relation with the early onset of puberty in girls. 6535 4259 695 11 15 5.8-12.2 2009/2010 2013/2014 2014-2017 Higher BMI during childhood is associated with early puberty. 2008 and 2009 2000-2002 Obesity during childhood is related to the earlier onset of puberty. Boys Girls 84 123 71 (Continues) 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 10 NIEUWENHUIS ET AL. 3.1 | Fat storage For the initiation of puberty, the timing of stimulation and/or inhibi- tion of different hormones is important, and additionally, a certain amount and distribution of body fat is needed in order to start menar- che, which emphasizes the importance of body fat. From an evolution- ary point of view, body fat increases in mammalian females during puberty onset, and it highlights the need to guarantee a healthy preg- 40 women with anorexia nervosa. particularly body fat localized predominantly on the gluteofemoral fat depots, is profoundly associated with start of menarche, more than nancy, offspring, and maternal survival. fat, sex-hormones, and neuroendocrine alterations can evolve in men- strual dysfunction, for instance, in women with severe obesity or in 41-43 44-46 to gluteofemoral fat depots suggesting that leptin may convey infor- amount of total body fat. mation on body fat distribution to the hypothalamus during puberty. An improper level of body Importantly, body fat distribution, Blood leptin levels are strongly related 45 3.2 | HPG axis The HPG axis is activated by the release of kisspeptin resulting in the release of GnRH from the hypothalamus, and LH and FSH from the pituitary gland. In girls, FSH is involved in the development of the folli- cles in the ovaries, and it promotes the secretion of estrogen. LH stim- ulates the production of androgen hormones and induces ovulation 48 9,47 the release of kisspeptin and neurokinin B, and kisspeptin thereby (Figure 1). The secretion of estrogen has an inhibitory effect on inhibits the GnRH release from the hypothalamus. pattern of GnRH is important for the regulation of the menstrual cycle. This roughly 28-day-cycle comprises several phases, including the follicular phase and luteal phase. During the follicular phase, increasing levels of FSH stimulate the maturation of follicles and the production of estrogen from the ovaries. This in turn inhibits the release of FSH from the pituitary gland. A high level of estrogen will induce the production of LH by the pituitary gland, resulting in ovula- tion. The matured follicle secretes progesterone thereby inhibiting the release of GnRH. When the corpus luteum is demolished, there is less 48 3.3 | Adipokines According to results from studies reported in Table 1, girls with obe- sity enter puberty earlier compared with girls with normal higher leptin concentrations inhibit the intake of food and increases inhibition of GnRH. As a consequence, the cycle will start again. whole process, starting from the activated HPG axis, results in the development of the secondary sex characteristics in girls including 9,47 thelarche and menarche. 13,14,16-23,49-51 weight. these girls might be found in the secretion of adipokines. For instance, leptin is positively associated with the amount of body fat. Generally, energy expenditure. 9,52-54 An explanation for the early onset of puberty in The expression This TABLE 1 (Continued) Authors Year Country Study Design Primary Outcome Sample Sex Size (n) Age (y) Data Collection Herman-Giddens et al28 2012 USA Cross-sectional Observed mean ages of beginning genital and pubic hair growth and early testicular volumes were earlier than in past studies, depending on the characteristic and race/ethnicity. Boys 4131 6-16 2005-2010 Sorensen et al29 Aksglaede et al30 2010 2009 Denmark Denmark Cross-sectional/longitudinal Longitudinal Puberty onset at earlier ages was associated with an increased BMI in boys. Boys 1528 5.8-19.9 1991-1993/2006-2008 1930-1969 Juul et al31 Ribeiro et al32 2007 2006 Denmark Portugal Retrospective cohort Cross-sectional Higher BMI is associated with early voice break. 11-15 10-15 1990-1999 Kaplowitz et al18 Abbreviation: BMI, body mass USA Cross-sectional The early onset of puberty in Caucasian girls is likely related to an increased BMI. 5-12 1992-1993 2001 index. The higher BMI in boys and girls at 7 y of age, the earlier they enter puberty. Boys 21 612 Girls 135 223 Boys 463 Boys 382 Girls 437 Girls 10 750 Early sexual maturation in boys and girls is associated with overweight. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 5 of 10 Leptin may possibly play a role in adrenarche as its plasma level increases with higher levels of body fat and as it can modulate both girls. 33 ing adrenarche. In coherence, in children with obesity, the androgen These findings suggested that lower reproductive status was associated with higher total adiponectin concentrations and that a higher reproductive status was related to higher HMW adiponectin the HPA and HPG axes. These axes are functionally integrated dur- DHEAS was positively associated with leptin levels. Nevertheless, concentrations in girls. In addition, individuals with obesity often another study showed that enhanced adrenal androgen secretion in girls with premature adrenarche was not explained by leptin or BMI 55 ated with androgen levels in girls ; however, it was not related to levels. and IL-6. TNF-α alters, and IL-6 inhibits the expression of 56 8 In addition, the adipokine adiponectin was negatively associ- 57 differences of adiponectin seem to develop during the progression of 56 adiponectin (Figure 2). Thereby, a low level of total adiponectin and/or high levels of inflammatory cytokines in individuals with obe- sity can promote the onset of puberty. Many more adipokines are secreted by WAT including omentin, 52,65-67 9,36,62,68 adrenarche in girls with Prader-Willi syndrome. Interestingly, sex puberty. adrenarche; however, both are not required factors. Thus, leptin and adiponectin might be able to influence In gonadarche, leptin can stimulate the secretion of kisspeptin, and subsequently activation of the HPG axis, which eventually increases the expression of estrogen and androstenedione in the ova- 58 2,60 65-67 The expression of these ries (Figure 2). Ob gene in WAT, resulting in the synthesis and secretion of leptin. Thus, high levels of leptin promote onset of puberty in girls via secre- tion of kisspeptin, and estrogen stimulates leptin secretion addition- ally. Moreover, adiponectin can affect the HPG axis due to the expression of adiponectin receptors in the hypothalamus, pituitary In return, estrogen stimulates the expression of the 59 gland, and gonads. onset as it inhibits the secretion of kisspeptin and GnRH in the hypo- thalamus and the release of GH and LH in the pituitary gland, and 2,60-62 52,60 63 girls with central precocious puberty (CPP). Moreover, total adiponectin had negative correlations with progression of puberty in girls (defined by Tanner stages), whereas HMW adiponectin had FIGURE 2 Adipokinesaffectingthe initiation of puberty in girls. Leptin stimulates the release of kisspeptin in KNDy neurons, which activates the hypothalamus to produce gonadotropin releasing hormone (GnRH). In response to the release of GnRH, the pituitary gland secretes follicle stimulating hormone (FSH) and luteinising hormone (LH), which stimulates the ovaries to release estrogen resulting in the formation of secondary sex characteristics in girls. Estrogen stimulates the production of leptin. Adiponectin inhibits GnRH release resulting in reduced levels of GnRH and thereby a delayed onset of puberty. TNF- α and IL-6 inhibit the production of adiponectin and therefore stimulate the onset of puberty In detail, adiponectin is a regulator of puberty thereby inhibiting the onset of puberty (Figure 2). with obesity often have low levels of adiponectin. et al. showed that total adiponectin was significantly lower, whereas high molecular weight (HMW) adiponectin was significantly higher in ment. 55 63 develop a chronic low-grade inflammatory state, which can be indi- cated by a high level of circulating inflammatory cytokines like TNF-α 64 Individuals Sitticharoon positive associations with LH levels and the progression of puberty in 63 visfatin, resistin, and chemerin. and visfatin are expressed in the ovaries. adipokines in the ovaries suggests a role within the reproductive sys- tem; however, the exact biological processes have to be examined. Thus, specifically leptin, adiponectin, and inflammatory cytokines pro- duced by WAT could be permissive key players during an early onset of puberty in girls with obesity. As an exception, HMW adiponectin seems to have a stimulatory effect on peripheral repro- ductive function as HMW is not able to cross the blood brain 63 barrier. 4 | Markers that are used to assess puberty onset in boys are THE ONSET OF PUBERTY IN BOYS spermarche, voice break, testicular volume, and pubic hair develop- 35 spermarche develop in the early stages of puberty onset, voice In women, omentin, chemerin, While pubic hair development, larger testicular volume, and 69 testicular volume increases, which occurs at an average age of break usually appears in later stages of puberty. Generally, first 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 10 NIEUWENHUIS ET AL. 11.9 years, followed by the development of pubic hair at 12.2 years of average, and lastly, boys experience spermarche around an aver- 55 related with leptin levels. Thereby, leptin plausibly has a minor impact in adrenarche in boys. Since leptin receptors are found in the hypothalamus, pituitary gland, and testes, they might be involved in the onset of puberty by affecting the HPG axis during gonadarche. Leptin stimulates the release of kisspeptin and GnRH, and as a consequence, it accelerates the onset of puberty (Table 1, Figure 3). In contrast, adiponectin inhibits the secretion of GnRH, GH, LH, and FSH therewith delaying the onset of puberty. However, adiponectin levels are generally lower in men compared with women and even lower in men with obe- age age of 13.4 years. 70 4.1 | Fat storage Many aspects of the reproductive physiology are energetically demanding,71 and therefore, an adequate energy level is necessary. In boys, a dynamic change in body composition occurs around the age of 10 to 13 years, in which they gain approximately 40% of sity. culating inflammatory cytokines. levels can stimulate the HPG axis and therewith an early onset of puberty in boys. Nevertheless, leptin can inhibit the production of tes- 72 mostly consisting of lean mass, which causes exhaustion of most of fat. Subsequently, a growth spurt follows in which they gain tissue 72 in boys, an adequate amount of body fat is important in the onset of their body fat. These alterations in amount of body fat indicate that 4.2 | Puberty in boys is initiated by the release of kisspeptin. As mentioned before, this activates the HPG axis, resulting in the release of GnRH from the hypothalamus, and consequently the release of LH and FSH 9,74 puberty. tosterone from the testes, to estrogen (Figure 3). of the development of secondary sex characteristics in boys. Additionally, leptin can affect fertility in men as it can modulate the nutritional support of spermatogenesis, and moreover, dysfunction of spermatogenesis is associated with an increased leptin level and 73 58 2,60-62 HPG axis from the pituitary gland (Figure 1). and LH stimulates the secretion of testosterone from the testes, which inhibits the release of kisspeptin from the KNDy neurons and 9,48 in men, the release of kisspeptin is more consistent, causing a con- 29,48 subsequently GnRH from the hypothalamus. receptors expressed on KNDy neurons. In humans, KNDy neurons Contrarily to women, LH-induced testosterone levels lead to the stant release of LH. development of secondary sex characteristics in boys. differences between sexes in kisspeptin release are related to a sex- specific and sex steroid-dependent kisspeptin system as estrogen and progesterone modulate kisspeptin activity through the sex-steroid 48 in the infundibular nucleus are involved in negative and positive sex- 48 tal exposure to sex steroids and result in sex-specific differences in steroid feedbacks. kisspeptin release. These sexual dimorphisms are induced by perina- 75,76 4.3 | Adipokines The association between obesity and puberty onset in boys is rather controversial compared with findings in girls. Most studies reported an early onset of puberty in boys associated with increased ate adipose tissue from actual breast tissue. stages are more difficult to assess than female stages as boys lack a more determined marker such as menarche. Thirdly, puberty onset can be indicated by the activation of the HPG axis, and the presence of these secondary sex characteristics is the result of hormonal 2 14,17,22,23,50,51,77,78 BMI, 20,49 all while others reported no associations at Current markers used 79 16,80 or a delayed onset of puberty (Table 1). The presence of excessive adipose tissue can be involved in puberty onset in boys as the secretion of adipokines can modulate both adrenarche and gonadarche. Leptin can affect adrenarche by modulating both the HPG and HPA axes,33 and moreover, androgen levels were positively 55 nal androgen secretion in boys with premature adrenarche was not associated with plasma leptin levels. Nevertheless, enhanced adre- 9 In more detail, 61,62 adiponectin, and individuals with obesity often have high levels of cir- Moreover, inflammatory cytokines, TNF-α, and IL-6, inhibit expression of the leptin receptor in the testis. FSH induces spermatogenesis, too. function and role still have to be examined. 64 High leptin and low adiponectin and fat tissue can convert testosterone Both processes might result in the delay 29,61,79 81,82 In men, other adipokines like chemerin are found in the gonads 65 Thus, particularly high leptin and low adiponectin levels stimulate the HPG axis and thereby accelerate the onset of puberty in boys. Additionally, leptin can dysregulate the development of secondary sex characteristics and spermatogenesis by affecting testosterone levels and nutritional sup- port of spermatogenesis. 5 | LIMITATIONS AND FUTURE RESEARCH DIRECTIONS Even though multiple epidemiological studies have shown the link between puberty onset and obesity, there are some important limita- tions. Firstly, determining both the onset and stage of puberty is rather difficult. For instance, assessing the stage of breast develop- ment in girls with obesity is complicated as clinicians should differenti- 2 changes in response to the activated HPG axis. to determine the onset of puberty refer to secondary sex characteris- tics, such as testicular volume in boys and breast development in girls. A more accurate measurement of puberty onset would be to combine secondary sex characteristics with plasma or serum hormone level measurements such as LH, FSH, adipokines, e.g. leptin. Thereby, differences in puberty measurements could explain variations in the age of puberty onset between boys and girls within different Thereby, resistin is expressed in the testes of rats, but its exact 83 Secondly, male pubertal 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 7 of 10 FIGURE 3 Adipokines affecting the initiation of puberty in boys. Leptin activates kisspeptin secretion in KNDy neurons, this activates the production of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH stimulates the pituitary gland to secrete follicle stimulating hormone (FSH) and luteinising hormone (LH), activating the production of testosterone from the testes allowing the development of secondary sex characteristics. Leptin also inhibits the production of testosterone, which may cause a delayed onset of puberty. Adiponectin inhibits GnRH release. Low levels of adiponectin, as a result of TNF-α and IL-6 expression, lead to a reduced inhibition of GnRH. In response to GnRH release, the pituitary gland will secrete FSH and LH, and the testes will produce testosterone resulting in the development of secondary sex characteristics in boys countries, and In addition, the inclusion of a of puberty. ferent time points is complicated, as subjects examined several decades ago presented pronounced differences concerning lifestyle patterns such as nutrition and exercise habits. Lastly, obesity or over- weight is often determined by BMI, a classification based on weight and height measurements. Additionally, it is important that all studies studies or across continents, ethnicities proper age range (8-16 years) is important when assessing the onset (Figure 4). 12-15,17,20-23,49,77-79,84,85 30,47 Furthermore, comparison between studies from dif- 86 Specifically in children, BMI is often dependent on age and growth use the same anthropometric standards and sex-specific cut-offs. 13,14,16-23,49-51,77-80 fat and would represent a more accurate measurement in its regard. Based on this review, several suggestions can be made for further research. Firstly, the roles of adipokines like resistin, chemerin, visfatin, and omentin in puberty onset, fertility, and sexual maturation should be examined in detail. Secondly, future research examining the onset of puberty should combine indicators of puberty onset (e.g. breast development or testicular volume) with plasma or serum hor- mone measurements such as LH, FSH, sex-steroids, adipokines (e.g. spurts. ment in case of growth spurts. distribution of body fat should be taken into account in determining puberty and obesity in children. For instance, the body adiposity index (BAI), which was introduced in 2011 by Bergman et al.,87 uses hip cir- cumference and height in order to estimate the percentage of body 87 Thereby, BMI is a less accurate measure- F I G U R E 4 87,88 Therefore, both percentage and Average age of puberty onset in Europe, China, and the United States according to several studies from Table 1. Age of puberty onset ranges from 8.47 to 13.33 years in girls and from 8.63 leptin), and body fat distribution (e.g. BAI,87 waist-hip ratio's and/or dual-energy X-ray absorptiometry (DXA)2). Additionally, defining con- sistent and general measurements of puberty in both boys and girls, combined with a proper age range (8-16 years), would facilitate the comparisons between different studies and their results. 12-15, 17, 20-23, 25-29, 31 to 13.7 years in boys. included if average age of markers used to assess puberty was not reported. Pink: girls. Blue: boys Studies (Table 1) were not 39, 56 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 8 of 10 NIEUWENHUIS ET AL. 6 | CONCLUSION In conclusion, epidemiological data regarding obesity and puberty onset in girls show similar outcomes as adiposity results in the early onset of puberty in girls. The majority of the studies examining boys with obesity indicate an early onset of puberty, while not all reported an earlier onset of puberty. In detail, high leptin, TNF-α, and IL-6 levels combined with low adiponectin levels stimulate the activation of the HPG axis in girls and boys with obesity, and 5, 45, 50, 51 REFERENCES 1. Kumar S, Kelly AS. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. May- o Clin Proc. 2017;92(2):251-265. 2. Reinehr T, Roth CL. Is there a causal relationship between obesity and puberty? The Lancet Child & adolescent health. 2019;3(1):44-54. 3. WorldHealthOrganization. Facts and figures on childhood obesity. 2017. 4. Guglielmi V, Sbraccia P. Obesity phenotypes: depot-differences in adipose tissue and their clinical implications. Eat Weight Disord. 2018; 23(1):3-14. 5. Gomez-Hernandez A, Beneit N, Diaz-Castroverde S. Escribano O. Dif- ferential role of adipose tissues in obesity and related metabolic and vas- cular complications. 2016;2016:1-15, 1216783. 6. Zwick RK, Guerrero-Juarez CF, Horsley V, Plikus MV. Anatomical, physiological, and functional diversity of adipose tissue. Cell Metab. 2018;27(1):68-83. 7. Gulyaeva O, Dempersmier J, Sul HS. Genetic and epigenetic control of adipose development. Biochimica et Biophysica Acta (BBA)— Molecular and Cell Biology of Lipids. 2019;1864:3-12. 8. Khan M, Joseph F. Adipose tissue and adipokines: the association with and application of adipokines in obesity. Forensic Sci. 2014;2014: 711-724, 328592. 9. Alotaibi MF. Physiology of puberty in boys and girls and pathological disorders affecting its onset. J Adolesc. 2019;71:63-71. 10. Cousminer DL, Stergiakouli E, Berry DJ, et al. Genome-wide associa- tion study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty. Hum Mol Genet. 2014;23(16):4452-4464. 11. Ahmed ML, Ong KK, Dunger DB. Childhood obesity and the timing of puberty. Trends in endocrinology and metabolism: TEM. 2009;20(5): 237-242. 12. Biro FM, Pajak A, Wolff MS, et al. Age of menarche in a longitudinal US cohort. J Pediatr Adolesc Gynecol. 2018;31(4):339-345. 13. Currie C, Ahluwalia N, Godeau E, Nic Gabhainn S, Due P, Currie DB. Is obesity at individual and national level associated with lower age at menarche? Evidence from 34 countries in the Health Behaviour in School-aged Children Study. The Journal of adolescent health: official publication of the Society for Adolescent Medicine. 2012;50(6): 621-626. 14. De Leonibus C, Marcovecchio ML, Chiavaroli V, de Giorgis T, Chiarelli F, Mohn A. Timing of puberty and physical growth in obese children: a longitudinal study in boys and girls. Pediatr Obes. 2014; 9(4):292-299. 15. Flom JD, Cohn BA, Tehranifar P, et al. Earlier age at menarche in girls with rapid early life growth: cohort and within sibling analyses. Ann Epidemiol. 2017;27(3):187-93.e2. 16. Glass NA, Torner JC, Letuchy EM, et al. The relationship between greater prepubertal adiposity, subsequent age of maturation, and bone strength during adolescence. Journal of bone and mineral research: the official journal of the American Society for Bone and Min- eral Research. 2016;31(7):1455-1465. 17. Holmgren A, Niklasson A, Nierop AF, et al. Pubertal height gain is inversely related to peak BMI in childhood. Pediatr Res. 2017;81(3): 448-454. 18. Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman- Giddens ME. Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics. 2001;108(2):347-353. 19. Kelly Y, Zilanawala A, Sacker A, Hiatt R, Viner R. Early puberty in 11-year-old girls: Millennium Cohort Study findings. Arch Dis Child. 2017;102(3):232-237. 20. Lazzeri G, Tosti C, Pammolli A, et al. Overweight and lower age at menarche: evidence from the Italian HBSC cross-sectional survey. BMC Womens Health. 2018;18(1):168-174. thereby an early onset of obesity. leptin can inhibit the production of testosterone in boys and subse- quently inhibit the development of secondary sex characteristics affecting spermatogenesis. for other adipokines, like resistin and omentin, are present in the testes and ovaries suggesting a role in puberty or reproduction; 58, 71 however, their plausible function is still unknown. that adipokines may be key regulators in an early onset of puberty in both girls and boys with obesity, specifically by affecting the HPG axis during gonadarche. Future research should focus on assessing puberty onset by measuring consistent puberty markers and determine the percentage of body fat and its distribution and adipokines and hormone serum levels particularly involved in the HPG axis. CONFLICTS OF INTEREST The authors declare no conflict of interest. FUNDING INFORMATION This research was funded by Europees Fonds voor Regionale Ontwikkeling (EFRO), project BriteN 2016. ORCID Ilse A.C. Arnoldussen Amanda J. Kiliaan https://orcid.org/0000-0002-7395-5284 https://orcid.org/0000-0002-2158-6210 13, 14, 16-26, 29-32 Furthermore, several receptors Nevertheless, We conclude Search strategy We searched PubMed for articles published before Novem- ber 15th, 2019 using relevant keywords, including ‘onset of puberty and adiposity/obesity’, ‘onset of puberty’, ‘children with obesity’, ‘adipose tissue’, ‘childhood obesity’, ‘adiposity’, ‘obesity’, ‘adipokine(s)’, ‘HPG axis’, ‘adipokines ovary/ova- ries’, or ‘adipokines testes’, either alone or in combination. Selection criteria used were English language, longitudinal or cross-sectional studies assessing the onset of puberty, including menarche, thelarche, spermarche, or voice break, combined with high BMI or obesity/adiposity, and articles assessing or reviewing adipokines and its effects on the reproductive system. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 9 of 10 21. Lian Q, Mao Y, Luo S, et al. Puberty timing associated with obesity and central obesity in Chinese Han girls. BMC Pediatr. 2019; 19(1):1-7. 22. Deng Y, Liang J, Zong Y, et al. Timing of spermarche and menarche among urban students in Guangzhou, China: trends from 2005 to 2012 and association with Obesity. Sci Rep. 2018;8(1):263-270. 23. Li W, Liu Q. Association of prepubertal obesity with pubertal devel- opment in Chinese girls and boys: a longitudinal study. 2018;30: e23195. 24. Mendle J, Beltz AM, Carter R, Dorn LD. Understanding puberty and its measurement: ideas for research in a new generation. Journal of research on adolescence: the official journal of the Society for Research on Adolescence. 2019;29(1):82-95. 25. Pagani S, Meazza C, Gertosio C, Bozzola E, Bozzola M. Growth hor- mone receptor gene expression in puberty. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2015;47:581-584. 26. Abreu AP, Kaiser UB. Pubertal development and regulation. Lancet Diabetes Endocrinol. 2016;4(3):254-264. 27. Aguirre RS, Eugster EA. Central precocious puberty: from genetics to treatment. Best Pract Res Clin Endocrinol Metab. 2018;32(4): 343-354. 28. Sultan C, Gaspari L, Maimoun L, Kalfa N, Paris F. Disorders of puberty. Best Pract Res Clin Obstet Gynaecol. 2018;48:62-89. 29. Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH path- way in human reproductive health and disease. Hum Reprod Update. 2014;20(4):485-500. 30. Dahl SK, Amstalden M, Coolen L, Fitzgerald M, Lehman M. Dynorphin immunoreactive fibers contact GnRH neurons in the human hypothal- amus. Reprod Sci. 2009;16(8):781-787. 31. Navarro VM, Gottsch ML, Chavkin C, Okamura H, Clifton DK, Steiner RA. Regulation of gonadotropin-releasing hormone secretion by kisspeptin/dynorphin/neurokinin B neurons in the arcuate nucleus of the mouse. J Neurosci. 2009;29(38):11859-11866. 32. Zhai L, Liu J, Zhao J, et al. Association of obesity with onset of puberty and sex hormones in chinese girls: a 4-year longitudinal study. PLoS ONE. 2015;10(8):1-12, e0134656. 33. Cizza G, Dorn LD, Lotsikas A, Sereika S, Rotenstein D, Chrousos GP. Circulating plasma leptin and IGF-1 levels in girls with premature adrenarche: potential implications of a preliminary study. Horm Metab Res. 2001;33(3):138-143. 34. Cousminer DL, Widén E, Palmert MR. The genetics of pubertal timing in the general population: recent advances and evidence for sex-spec- ificity. Curr Opin Endocrinol Diabetes Obes. 2016;23(1):57-65. 35. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44(235):291-303. 36. Lacroix AE, Whitten R. Physiology. Treasure Island (FL): Menarche. StatPearls. StatPearls Publishing; 2018. 37. McDowell MA, Brody DJ, Hughes JP. Has Age at Menarche Chan- ged? Results from the National Health and Nutrition Examination Sur- vey (NHANES) 1999–2004. J Adolesc Health. 2007;40(3):227-231. 38. de Muinich Keizer SM, Mul D. Trends in pubertal development in Europe. Hum Reprod Update. 2001;7(3):287-291. 39. Talma H, Schönbeck Y, van Dommelen P, Bakker B, van Buuren S, Hirasing RA. Trends in menarcheal age between 1955 and 2009 in the Netherlands. PLoS ONE. 2013;8:e60056-e60056. 40. Kaplan HS, Lancaster JB. An evolutionary and ecological analysis of human fertility, mating patterns, and parental investment. Off- spring: Human fertility behavior in biodemographic perspective. 2003;1: 170-223. 41. Mitan LA. Menstrual dysfunction in anorexia nervosa. J Pediatr Adolesc Gynecol. 2004;17(2):81-85. 42. Xu H, Li P-H, Barrow TM, et al. Obesity as an effect modifier of the association between menstrual abnormalities and hypertension in young adult women: Results from Project ELEFANT. PLoS ONE. 2018; 13(11):e0207929-e0207929. 43. Tauqeer Z, Gomez G, Stanford FC. Obesity in women: insights for the clinician. J Womens Health (Larchmt). 2018;27(4):444-457. 44. de Ridder CM, Thijssen JH, Bruning PF, Van den Brande JL, Zonderland ML, Erich WB. Body fat mass, body fat distribution, and pubertal development: a longitudinal study of physical and hormonal sexual maturation of girls. J Clin Endocrinol Metab. 1992;75(2): 442-446. 45. Lassek W, Gaulin S. Brief communication: menarche is related to fat distribution. Am J Phys Anthropol. 2007;133(4):1147-1151. 46. Loomba-Albrecht LA, Styne DM. Effect of puberty on body composi- tion. Curr Opin Endocrinol Diabetes Obes. 2009;16:10-15. 47. Simonneaux V, Bahougne T. A multi-oscillatory circadian system times female reproduction. Front Endocrinol. 2015;6:1-15. 48. Marques P, Skorupskaite K, George JT, Anderson RA. Physiology of GNRH and gonadotropin secretion. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. Endotext.org: South Dartmouth (MA); 2000. 49. Barcellos Gemelli IF, Farias EDS, Souza OF. Age at menarche and its association with excess weight and body fat percentage in girls in the Southwestern Region of the Brazilian Amazon. J Pediatr Adolesc Gynecol. 2016;29(5):482-488. 50. Aksglaede L, Juul A, Olsen LW, Sorensen TI. Age at puberty and the emerging obesity epidemic. PLoS ONE. 2009;4:1-6, e8450. 51. Ribeiro J, Santos P, Duarte J, Mota J. Association between over- weight and early sexual maturation in Portuguese boys and girls. Ann Hum Biol. 2006;33(1):55-63. 52. Budak E, Fernandez Sanchez M, Bellver J, Cervero A, Simon C, Pellicer A. Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system. Fertil Steril. 2006;85(6):1563-1581. 53. Castellano JM, Tena-Sempere M. Metabolic control of female puberty: potential therapeutic targets. Expert Opin Ther Targets. 2016; 20(10):1181-1193. 54. Venancio JC, Margatho LO, Rorato R, et al. Short-term high-fat diet increases leptin activation of CART neurons and advances puberty in female mice. Endocrinology. 2017;158(11):3929-3942. 55. l'Allemand D, Schmidt S, Rousson V, Brabant G, Gasser T, Gruters A. Associations between body mass, leptin, IGF-I and circulating adrenal androgens in children with obesity and premature adrenarche. Eur J Endocrinol. 2002;146(4):537-543. 56. Böttner A, Jr K, Müller G, et al. Gender Differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metabol. 2004;89(8):4053- 4061. 57. Unanue N, Bazaes R, Iñiguez G, Cortes F, Avila A, Mericq V. Adre- narche in Prader-Willi syndrome appears not related to insulin sensi- tivity and serum adiponectin. Horm Res. 2007;67(3):152-158. 58. Michalakis K, Mintziori G, Kaprara A, Tarlatzis BC, Goulis DG. The complex interaction between obesity, metabolic syndrome and repro- ductive axis: a narrative review. Metabolism: clinical and experimental. 2013;62(4):457-478. 59. Machinal-Quelin F, Dieudonne MN, Pecquery R, Leneveu MC, Giudicelli Y. Direct in vitro effects of androgens and estrogens on ob gene expression and leptin secretion in human adipose tissue. Endo- crine. 2002;18(2):179-184. 60. Dobrzyn K, Smolinska N, Kiezun M. Adiponectin: A new regulator of female reproductive system. Int J Endocrinol. 2018;2018:1-12, 7965071. 61. Martin LJ. Implications of adiponectin in linking metabolism to testic- ular function. Endocrine. 2014;46(1):16-28. 62. Mathew H, Castracane VD, Mantzoros C. Adipose tissue and repro- ductive health. Metabolism: clinical and experimental. 2018;86:18-32. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 10 of 10 NIEUWENHUIS ET AL. 63. Sitticharoon C, Sukharomana M, Likitmaskul S, Churintaraphan M, Maikaew P. Corrigendum to: Increased high molecular weight adiponectin, but decreased total adiponectin and kisspeptin, in central precocious puberty compared with aged-matched prepubertal girls. Reprod Fertil Dev. 2017;29:2506-2517. 64. Das UN. Is obesity an inflammatory condition? Nutrition. 2001; 17(11-12):953-966. 65. Comninos AN, Jayasena CN, Dhillo WS. The relationship between gut and adipose hormones, and reproduction. Hum Reprod Update. 2014; 20(2):153-174. 66. Singh A, Choubey M, Bora P, Krishna A. Adiponectin and chemerin: contrary adipokines in regulating reproduction and metabolic disor- ders. Reproductive sciences (Thousand Oaks, Calif). 2018;25:1462- 1473. 67. Tsatsanis C, Dermitzaki E, Avgoustinaki P, Malliaraki N, Mytaras V, Margioris AN. The impact of adipose tissue-derived factors on the hypothalamic-pituitary-gonadal (HPG) axis. Hormones (Athens). 2015; 14:549-562. 68. Kang MJ, Oh YJ, Shim YS, Baek JW, Yang S. Hwang IT. The usefulness of circulating levels of leptin, kisspeptin, and neurokinin B in obese girls with precocious puberty. 2018;34:627-630. 69. Lee J, Song J, Hootman JM, et al. Obesity and other modifiable fac- tors for physical inactivity measured by accelerometer in adults with knee osteoarthritis: data from the osteoarthritis initiative (OAI). Arthritis Care Res (Hoboken). 2012;53-61. 70. Bramswig J, Dubbers A. Disorders of pubertal development. Deutsches Arzteblatt international. 2009;106:295-303. quiz 04 71. Elias CF, Purohit D. Leptin signaling and circuits in puberty and fertil- ity. Cell Mol Life Sci. 2013;70(5):841-862. 72. Riumallo J, Durnin JV. Changes in body composition in adolescent boys. Eur J Clin Nutr. 1988;42(2):107-112. 73. Siervogel RM, Demerath EW, Schubert C, et al. Puberty and body composition. Horm Res. 2003;60(Suppl 1):36-45. 74. Zhang J. Gong M. Andrologia: Review of the role of leptin in the regu- lation of male reproductive function; 2018. 75. Kauffman AS, Gottsch ML, Roa J, et al. Sexual differentiation of Kiss1 gene expression in the brain of the rat. Endocrinology. 2007;148(4): 1774-1783. 76. Zeydabadi Nejad S, Ramezani Tehrani F, Zadeh-Vakili A. The role of kisspeptin in female reproduction. Int J Endocrinol Metab. 2017;15:1- 11, e44337. 77. Sorensen K, Aksglaede L, Petersen JH, Juul A. Recent changes in pubertal timing in healthy Danish boys: associations with body mass index. J Clin Endocrinol Metab. 2010;95(1):263-270. 78. Juul A, Magnusdottir S, Scheike T, Prytz S, Skakkebaek NE. Age at voice break in Danish boys: effects of pre-pubertal body mass index and secular trend. Int J Androl. 2007;30(6):537-542. 79. Lee JM, Wasserman R, Kaciroti N, et al. Timing of puberty in overweight versus obese boys. Pediatrics. 2016;137(2):137-146, e20150164. 80. He F, Guan P, Liu Q, Crabtree D, Peng L, Wang H. The relationship between obesity and body compositions with respect to the timing of puberty in Chongqing adolescents: a cross-sectional study. BMC Pub- lic Health. 2017;17:664-673. 81. Ishikawa T, Fujioka H, Ishimura T, Takenaka A, Fujisawa M. Expres- sion of leptin and leptin receptor in the testis of fertile and infertile patients. Andrologia. 2007;39(1):22-27. 82. Martins AD, Moreira AC, Sa R, et al. Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility? Biochim Biophys Acta. 1852;2015: 1824-1832. 83. Morash BA, Willkinson D, Ur E, Wilkinson M. Resistin expression and regulation in mouse pituitary. FEBS Lett. 2002;526(1-3):26-30. 84. Cabrera SM, Bright GM, Frane JW, Blethen SL, Lee PA. Age of thelarche and menarche in contemporary US females: a cross- sectional analysis. Journal of pediatric endocrinology & metabolism: JPEM. 2014;27(1-2):47-51. 85. Herman-Giddens ME, Steffes J, Harris D, et al. Secondary sexual characteristics in boys: data from the Pediatric Research in Office Settings Network. Pediatrics. 2012;130(5):e1058-e1068. 86. WHO. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1995;854:1-452. 87. Akin I, Tolg R, Hochadel M, et al. No evidence of “obesity paradox” after treatment with drug-eluting stents in a routine clinical practice: results from the prospective multicenter German DES.DE (German Drug-Eluting Stent) Registry. JACC Cardiovasc Interv. 2012;5(2): 162-169. 88. Marcovecchio ML, Chiarelli F. Obesity and growth during childhood and puberty. World Rev Nutr Diet. 2013;106:135-141. How to cite this article: Nieuwenhuis D, Pujol-Gualdo N, Arnoldussen IAC, Kiliaan AJ. Adipokines: A gear shift in puberty. 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