major hormones they produce Formore indepth information on thosehorm - PDF document

major hormones they produce. Formore in-depth information on thosehormones, the reader should consultstanti et al. 1998; Wilson et al. 1998).Finally, the article presents variousproduced in several organs cooperateto achieve the desired regulatory effects.the system responses in normal, healthypeople. For information regardingsystems, the reader is referred to sub-sequent articles in this issue of AlcoholHealth & Research World . What Are Hormones? Hormones are molecules that are pro-duced by endocrine glands, includingthe hypothalamus, pituitary gland,adrenal glands, gonads, (i.e., testes and ovaries), thyroid gland, parathyroidglands, and pancreas (see figure 1). Theterm response to specific stimuli, the productsof those glands are released into thebloodstream.The hormones then arecells. Some hormones have only a fewspecific target cells, whereas otherhormones affect numerous cell typesthroughout the body. The target cellsfor each hormone are characterized bythe presence of certain docking mole-cules (i.e., receptors) for the hormonethat are located either on the cell surfacebetween the hormone and its receptortriggers a cascade of biochemical reac-tions in the target cell that eventuallys function or activity. Mechanisms of Action Several classes of hormones exist, includ-ing steroids, amino acid derivatives,and polypeptides and proteins. Thosehormone classesdiffer in their general molecular structures (e.g., size andchemical properties). As a result of thestructural differences, their mechanismstheir target cells and how they modulatethe activity of those cells) also differ.Steroids, which are produced by thegonads and part of the adrenal gland(i.e., the adrenal cortex), have a molecularstructure similar to that of cholesterol.cells and interact with receptors in thereceptor complexes then bindto cerregions of the cellthe DNA), thereby regulating the activ-ityof specific hormone-responsive genes.Amino acid derivatives are modi-fied versions of some of the buildingblocks of proteins. The thyroid glandand another region of the adrenalglands (i.e., the adrenal medulla) pro-amino acid derivatives). Like steroids,amino acid derivatives can enter the 154 1and salivary glands) release their secretions to the Hypothalamus Pituitary gland Thyroid glandParathyroid glandTestis (in male)Pancreas(Islets of Adrenal gland (in female) (i.e., endocrine) organs in the body. (For the purposes of illustration, both cell, where they interact with receptorproteins that are already associatedwith specific DNA regions. ThePolypeptide and protein hormonesare chains of amino acids of variouslengths (from three to several hundredamino acids). These hormones arepituitary gland, and pancreas. In someinstances, they are derived from inactiveprecursors, or pro-hormones, whichcan be cleaved into one or more activehormones. Because of their chemicalstructure, the polypeptide and proteinhormones cannot enter cells. Instead,they interact with receptors on thecell surface. The interaction initiatesmembrane or interior, eventually mod-ifyingthe cell Regulation of Hormone Activity To maintain the bodyand respond appropriately to changesin the environment, hormone produc-tion and secretion must be tightlycontrolled. To achieve this control,many bodily functions are regulatednot by a single hormone but by severalhormones that regulate each other (see figure 2). For example, for manysecretes so-called releasing hormones,which are transported via the blood tothe pituitary gland. There, the releasinghormones induce the prod

uction andsecretion of pituitary hormones, whichin turn are transported by the blood totheir target glands (e.g., the adrenalglands, gonads, or thyroid). In thoseglands, the interaction of the pituitaryhormones with their respective targetcells results in the release of the hormonestargeted by the hormone cascade. Constant feedback from the targetglands to the hypothalamus and pitu-itary gland ensures that the activity ofthe hormone system involved remainswithin appropriate boundaries. Thus,in most cases, negative feedback mech-anisms exist by which hormonesreleased by the target glands affectthe pituitary gland and/or hypo-figure 2). When certainpredeterminedblood levels of thosehormones are reached, the hypothala-mus and/or the pituitary ceaseshormone release, thereby turning off the cascade. In some instances, aso-calledshort-loop feedback occurs,in which pituitary hormones directlynegative feedback systems operate(i.e., the target hormone levels thatare required to turn off hypothor pituitary hormonerelease) canchange at different physiological statesor stages of life. For example, theprogressive reduction in sensitivity of the hypothalamus and pituitary tonegative feedback by gonadal steroidhormones plays an important role inAlthough negative feedback ismore common, some hormone systems are controlled by positivethe hypothalamus and/or pituitary to increase the release of hormonesthat stimulate the secretion of thetarget gland hormone. One suchmenstrual period: Increasing estrogenlevels in the blood temporarily release from the pituitary and hypo-thalamus, thereby further increasing Vol. 22, No. 3, 1998155 The Endocrine System Releasing hormonePituitary hormoneTarget gland hormoneShort-loop feedback Figure 2 Schematic representation of negative feedback mechanisms that controlendocrine system activity. In many cases, the hormones released from the NOTE:+ = stimulates; Ð = inhibits. 156 Hormones Produced by the Major Hormone-Producing (i.e., Endocrine) Glands and Their Primary Functions Endocrine GlandHormonePrimary Hormone Function HypothalamusCorticotropin-releasing hormone (CRH)Stimulates the pituitary to release adrenocorticotropicGonadotropin-releasing hormone (GnRH)Stimulates the pituitary to release luteinizing hormone Thyrotropin-releasing hormone (TRH)Stimulates the pituitary to release thyroid-stimulating Growth hormone-releasing hormone Stimulates the release of growth hormone (GH) from the(GHRH)pituitarySomatostatinInhibits the release of GH from the pituitaryDopamineInhibits the release of prolactin from the pituitaryAnterior pituitary glandACTHLHIn women, stimulates the production of sex hormones (i.e.,FSHIn women, stimulates follicle development; in men, stimu-TSHStimulates the release of thyroid hormoneGHPromotes the bodyProlactinControls milk production (i.e., lactation)VasopressinHelps control the bodyOxytocinPromotes uterine contraction during labor and activatesAdrenal cortexCortisolAldosteroneHelps control the bodyTestesTestosteroneStimulates development of the male reproductive organs,OvariesEstrogen (produced by the follicle)Stimulates development of the female reproductive organsProgesterone (produced by the Prepares uterus for pregnancy and mammary glands for corpus luteum) lactationThyroid glandThyroid hormone (i.e., thyroxine [T] Controls metabolic processes in all cellsControls metabolic processes in all cells3]) CalcitoninHelps control calcium metabolism (i.e., lowers calcium Parathyroid glandParathyroid hormone (PTH)Helps control calcium metabolism (i.

e., increases calciumPancreasInsulinHelps control carbohydrate metabolism (i.e., lowers bloodGlucagonHelps control carbohydrate metabolism (i.e., increases estrogen levels and eventually lead-ing to ovulation. Such a mechanismrequires a specific threshold level,however, at which the positive feed-back loop is turned off in order to The Hypothalamus and Its Hormones The hypothalamus is a small regionlocated within the brain that controlsand behaviors, blood pressure and heartrate, body temperature maintenance,the sleep-wake cycle, and emotionalstates (e.g., fear, pain, anger, and pleasure). Hypothalamic hormonesplay pivotal roles in the regulation ofBecause the hypothalamus is part ofthe central nervous system, the hypothal-actually are producedby nerve cells (i.e.,neurons). In addition,because signals from other neuronscan modulate the release of hypothal-serves as the major link between thenervous and endocrinesystems. Forexample, the hypothalamus receivesinformation from higher brain centersthat respond to various environmentalsignals. Consequently, hypothalamicfunction is influenced by both theexternal and internal environments aswell as by hormone feedback. Stimulifrom the external environment thatindirectly influence hypothalamicfunction include the light-dark cycle;temperature; signals from other membersand a wide varietyof visual, auditory, olfactory, and sensorystimuli. The communication betweenother brain areas and the hypothalamus,which conveys information about theinternal environment, involves electro-chemical signal transmission throughmolecules called neurotransmitters (e.g., aspartate, dopamine, gamma-aminobutyric acid, glutamate, norepin-ephrine, and serotonin). The complexinterplay of the actions of variousneurotransmitters regulates the pro-duction and release of hormones fromThe hypothalamic hormones arereleased into blood vessels that connectthe hypothalamus and the pituitaryphyseal portal system). Because theygenerallypromote or inhibit the releaseof hormones from the pituitary gland,hypothalamic hormones are commonlycalled releasing or inhibiting hormones.The major releasing and inhibitinghormones include the following (alsosee table, p. 156):Corticotropin-releasing hormone(CRH), which is part of the hormonesystem regulating carbohydrate, pro-tein, and fat metabolism as well asGonadotropin-releasing hormone(GnRH), which helps controlsexual and reproductive functions,including pregnancy and lactation(i.e., milk production)Thyrotropin-releasing hormone(TRH), which is part of the hormonesystem controlling the metabolicprocesses of all cells and which con-tributes to the hormonal regulationof lactationGrowth hormone-releasing hor-promoting the organisms growthSomatostatin, which also affects boneand muscle growth but has theDopamine, a substance that functionsprimarily as a neurotransmitter butsuch as repressing lactation until itis needed after childbirth. The Pituitary and Its Major Hormones The pituitary (also sometimes calledsize of a small marble and is locatedin the brain directly below thehypothalamus. The pituitary glandconsists of two parts: the anteriorpituitary and the posterior pituitary. The Anterior Pituitary The anterior pituitary produces severalimportant hormones that either stimu-latetarget glands (e.g., the adrenalglands, gonads, or thyroid gland) toproduce target gland hormones ordirectly affect target organs. The pituitary hormones include adreno-corticotropic hormone (ACTH);gonadotropins; thyroid-stimulatinghormone (TSH), also called thyrotropin;

growth hormone (GH); and prolactin.The first three of those hormonesACTH, gonadotropins, and TSHact on other glands. Thus, ACTHstimulates the adrenal cortex to pro-duce corticosteroid hormonesprimarily cortisolas well as smallmones. The gonadotropins comprise(FSH). These two hormones regulatethe production of female and male sexhormones in the ovaries and testes aswell as the production of the germthat is, the egg cells (i.e., ova)and sperm cells (i.e., spermatozoa).TSH stimulates the thyroid gland toproduce and release thyroid hormone.The remaining two pituitary hormones,GH and prolactin, directly affect their Growth Hormone. abundant of the pituitary hormones.As the name implies, it plays a pivotalrole in controlling the bodys growthand development. For example, itstimulates the linear growth of thebones; promotes the growth of inter-connective tissue, endocrine glands,and muscle; and controls the devel-opment of the reproductive organs.Accordingly, the GH levels in the blood are highest during earlychildhood and puberty and declinethereafter. Nevertheless, even rela-tively low GH levels still may beimportant later in life, and GH The Endocrine System 157 In addition to its growth-promotingrole, GH affects carbohydrate, pro-Thus, GH increases the levels of thesugar glucose in the blood by reducingglucose uptake by muscle cells andadipose tissue and by promoting glu-cose production (i.e., gluconeogene-sis) from precursor molecules in theliver. (These actions are opposite toThe Pancreasand Its Hormones, p. 160.) GH alsofrom the blood into cells, as well astheir incorporation into proteins, andstimulates the breakdown of lipids inTo elicit these various effects, GHmodulates the activities of numeroustarget organs, including the liver, kid-neys, bone, cartilage, skeletal muscle,and adipose cells. For some of theseeffects, GH acts directly on the targetcells. In other cases, however, GH actsindirectly by stimulating the produc-growth factor 1 (IGF-1) in the liverports IGF-1 to the target organs,where it binds to specific receptors onlead to the increased DNA produc-the growth process.Two hypothalamic hormones con-trol GH release: (1) GHRH, whichstimulates GH release, and (2) somato-statin, which inhibits GH release. Thisregulatory mechanism also involves ashort-loop feedback component, byto stimulate somatostatin release. Inaddition, GH release is enhanced bystress, such as low blood sugar levels(i.e., hypoglycemia) or severe exercise,and by the onset of deep sleep. Acute and chronic alcohol consump-tion have been shown to reduce the levelseffects have been observed in animals aswell as in humans. Acute alcohol admin-istration also reduces GH secretion inresponse to other stimuli that normallyenhance the hormones release. Thosedeleteriouseffects of alcohol may beparticularly harmful to adolescents, whorequire GHfor normal developmentand puberty. (For more information ons effects on puberty and growth,see the article by Dees and colleagues,pp. 165 Prolactin. Together with other hor-mones, prolactin plays a central rolein the development of the female breastof lactation after childbirth. Prolactinfunction in men, however, is not wellunderstood, although excessive prolactinrelease can lead to reduced sex drive (i.e.,libido) and impotence. Several factorscontrol prolactin release from the ante-riorpituitary. For example, prolactinis released in increasing amounts inresponse to the rise in estrogen levelsin the blood that occurs during preg-nancy. In nursing women, prolactin isreleased in resp

onse to suckling by theinfant. Several releasing and inhibitoryfactors from the hypothalamus alsocontrol prolactin release. The mostimportant of those factors is dopamine,which has an inhibitory effect.Alcohol consumption by nursingthrough its effects on the release ofprolactin and oxytocin (see the follow-ing section) and through its effects onthe milk-producing (i.e., mammary)(For more information on alcoholon lactation, see the article by Heil andSubramanian, pp. 178 The Posterior Pituitary The posterior pituitary does not produceits own hormones; instead,it stores two hormonesvasopressinand oxytocinthat are produced by neurons in the hypothalamus.of the neurons, which are located the posterior pituitary.Vasopressin, also called arginine vaso-pressin (AVP), plays an important roles water and electrolyte econ-omy. Thus, AVP release promotes thereabsorption of water from the urinein the kidneys. Through this mech-anism, the body reduces urine volumeand conserves water. AVP release fromthe pituitary is controlled by the con-centration of sodium in the blood as wellas by blood volume and blood pressure.For example, high blood pressure orincreased blood volume results in theinhibition of AVP release. Consequently,more water is released with the urine,and both blood pressure and bloodvolume are reduced. Alcohol also hasbeen shown to inhibit AVP release.Conversely, certain other drugs (e.g.,nicotine and morphine) increase AVPrelease, as do severe pain, fear, nausea,and general anesthesia, thereby result-ing in lower urine production andwater retention.stored in the posterior pituitary, stim-ulates the contractions of the uterusduring childbirth. In nursing women,the hormone activates milk ejectionin response to suckling by the infant(i.e., the so-called let-down reflex). The Adrenal Glands and Their Hormones The adrenal glands are small structureslocated on top of the kidneys. Struct-urally, they consist of an outer layer(i.e., the cortex) and an inner layer(i.e., the medulla). The adrenal cortexproduces numerous hormones, primar-ilycorticosteroids (i.e., glucocorticoidsand mineralocorticoids). The cortex isalso the source of small amounts ofsex hormones; those amounts, however,are insignificant compared with theamounts normally produced by theovaries and testes. The adrenal medullaadrenalineand noradrenalinethat are releasedas part of the fight-or-flight responseto various stress factors.The primary glucocorticoid inhumans is cortisol (also called hydro-cortisone), which helps control carbo-hydrate, protein, and lipid metabolism.For example, cortisol increases glucoselevels in the blood by stimulating glu-coneogenesis in the liver and promotesthe formation of glycogen (i.e., a mole-cule that serves as the storage form ofglucose) in the liver. Cortisol also reducestissue, thereby opposing the effects of 158 insulin. Furthermore, in various tissues,cortisol promotes protein and lipidbreakdown into products (i.e., aminoacids and glycerol, respectively) that canIn addition to those metabolic activ-ities, cortisol appears to protect thevarious stress factors, including acutetrauma, major surgery, severe infections,pain, blood loss, hypoglycemia, andemotional stress. All of these stressfactors lead to drastic increases in thecortisol levels in the blood. For peoplein whom cortisol levels cannot increase(e.g., because they had their adrenalglands removed), even mild stress can be fatal. Finally, high doses of cortisol and other corticosteroids canbe used medically to suppress tissueinflammation i

n response to injuriesand to reduce the immune responseto foreign molecules. The primary mineralocorticoid inhumans is aldosterone, which alsohelps regulate the bodyelectrolyte balance. Its principal func-tions are to conserve sodium and toexcrete potassium from the body. Forexample, aldosterone promotes thereabsorption of sodium in the kidney,thereby reducing water excretion andincreasing blood volume. Similarly, aldo-sterone decreases the ratio of sodiumto potassium concentrations in sweatand saliva, thereby preventing sodiumloss via those routes. The effect can behighly beneficial in hot climates, wheremuch sweating occurs. In contrast to the glucocorticoids,pituitary, or hypothalamic, hormonesdo not regulate aldosterone release.Instead, it is controlled primarily byanother hormone system, the renin-angiotensin system, which also controlskidney function. In addition, the levelsinfluence aldosterone levels. The Gonads and Their Hormones The gonads (i.e., the ovaries and testes)serve two major functions. First, theyproduce the germ cells (i.e., ova inthe ovaries and spermatozoa in thetestes). Second, the gonads synthesizesteroid sex hormones that are necessaryfor the development and function ofboth female and male reproductiveorgans and secondary sex characteris-tics(e.g., the adult distribution ofbody hair, such as facial hair in men)as well as for pregnancy, childbirth,and lactation. Three types of sexhormones exist; each with differentfunctions: (1) estrogens (e.g., estradiol),which exert feminizing effects; (2)progestogens (e.g., progesterone),which affect the uterus in preparationfor and during pregnancy; and (3)androgens (e.g., testosterone), whichexert masculinizing effects. In additionto the reproductive functions, sexhormones play numerous essentialroles throughout the body. For exam-ple,they affect the metabolism ofcarbohydrates and lipids, the cardio-vascular system, and bone growthand development. Estrogens The major estrogen is estradiol, which,in addition to small amounts of estroneand estriol, is produced primarily inthe ovaries. Other production sites ofestrogens include the corpus luteum,the placenta, and the adrenal glands.In men and postmenopausal women,most estrogens present in the circula-tion are derived from the conversionof testicular, adrenal, and ovarianandrogens. The conversion occurs inperipheral tissues,primarily adiposeThe main role of estrogens is to coor-dinate the normal development andbreasts. During puberty, estrogens pro-mote the growth of the uterus, breasts,and vagina; determine the pattern ofbody that results in the typical femaleshape; regulate the pubertal growthspurt and cessation of growth at adultheight; and control the developmentof secondary sexual characteristics. Inadult women, the primary functionsof estrogens include regulating themenstrual cycle, contributing to thehormonal regulation of pregnancy andlactation, and maintaining female libido.(For more information on the menstrualcycle and alcoholarticle by Dees and colleagues, pp. 165169. For more information on alcoholeffects on the developing fetus, see thearticle by Gabriel and colleagues, pp.During menopause, estrogen pro-ductionin the ovaries ceases. The result-ing reduction in estrogen levels leads tosymptoms such as hot flashes, sweating,pounding of the heart (i.e., palpitations),increased irritability, anxiety, depression,and brittle bones (i.e., osteoporosis). Theadministration of estrogens(i.e., hormonereplacement therapy) canalleviate thosesymptoms and reduce theporosis and co

ronary heartdisease inpostmenopausal women. At the sametime, however, hormone replacementtherapy may increase the risk of certaintypes of cancer (e.g., breasteastcancer).Alcohol consumption has beenshownto increase estrogen levels in the bloodand urine, even in premenopausalper day (Reichman et al. 1993) and inthan one drink per day (Gavaler andVan Thiel 1992). These findings suggesthelp prevent osteoporosis and coronaryheart disease in postmenopausal women.Other studies,however, have no consistent association between alc-holconsumption and increased estrogenlevels (Dorgan et al. 1994; Purohit 1998).(For more information on the effects ofthe articles by Longnecker and Tseng,pp. 185189, and Gavaler, pp. 220 Progestogens The ovaries produce progestogens dur-inga certain phase of the menstrualcycle and in the placenta for most ofpregnancy. Progestogens cause changesin the uterine lining in preparationfor pregnancy andtogether withestrogensulate the developmentof the mammary glands in the breasts The Endocrine System 159 2from the follicle that releases the ovum during a in preparation for lactation. The pri-mary progestogen is progesterone. Androgens The principal androgenic steroid is tes-tosterone, which is secreted primarilyfrom the testes but also, in smallamounts, from the adrenal glands (bothin men and women) and from theovaries. Its main function is to stimulatethe development and growth of the malegenital tract. In addition, testosteronehas strong protein anabolic activitiesthat is, it promotes protein generation,which leads to increased muscle mass.The specific functions of testosteronevary during different developmentalstages, as follows:In the fetus, testosterone primarilyensures the development of theDuring puberty, testosterone pro-motes the growth of the male sexorgans and is responsible for othermale developmental characteristics,such as the pubertal growth spurtand eventual cessation of growth atadult height; deepening of the voice;growth of facial, pubic, axillary, andbody hair; and increase in muscular-ity and strengthIn the adult male, testosterone pri-marily serves to maintain masculinity,libido, and sexual potency as well asregulate sperm production. Testos-terone levels decline slightly withage, although the drop is not as dras-ticas the reduction in estrogen levelsin women during menopause. (Forinformation on alcoholmale reproduction, see the article byEmanuele and Emanuele, pp.195 The Thyroid and Its Hormones The thyroid gland, which consists of twolobes, is located in front of the windpipe(i.e., trachea), just below the voice box(i.e., larynx). The gland produces twostructurally related hormones, thyroxine) and triiodothyronine (Tare iodinated derivatives of the aminoacid tyrosine. Both hormones are collec-tively referred to as thyroid hormone.constitutes approximately 90 percentof the hormone produced in the thyroidgland. However, Tis a much moreactive hormone, and most of the Tproduced by the thyroid is convertedin the liver and kidneys.Thyroid hormone in general serves toincrease the metabolism of almost all bodytissues. For example, thyroid hormonestimulates the production of certain pro-teins involved in heat generation in thebody, a function that is essential for main-taining body temperature in cold climates.Moreover, thyroid hormone promotesseveral other metabolic processes involv-ing carbohydrates, proteins, and lipidsthat help generate the energy requireds functions. In addition tothose metabolic effects, thyroid hormoneplays an essential role in the devel

opmentof the central nervous system during latefetal and early postnatal developmentalstages. Furthermore, thyroid hormoneexerts an effect similar to that of GH onnormal bone growth and maturation.Finally, thyroid hormone is required forthe normal development of teeth, skin,and hair follicles as well as for the func-tioning of the nervous, cardiovascular,and gastrointestinal systems.In addition to thyroid hormone, cer-taincells (i.e., parafollicular C cells) inthe thyroid gland produce calcitonin, acalcium levels in the blood. Specifically,calcitonin lowers calcium levels in theblood by reducing the release of calciumfrom the bones; inhibiting the constanterosion of bones (i.e., bone resorption),which also releases calcium; and inhibitingthe reabsorption of calcium in the kidneys.Those effects are opposite to those ofparathyroid hormone (PTH), which isdiscussed in the following section. The Parathyroid Glands and Their Hormones The parathyroid glands are four pea-sized bodies located behind the thyroidgland that produce PTH. This hormoneincreases calcium levels in the blood,needed for numerous functions through-outthe body (e.g., muscle movementSpecifically, PTH causes reabsorptionof calcium from and excretion of phos-phate in the urine. PTH also promotesthe release of stored calcium from thebones as well as bone resorption, bothof which increase calcium levels in theblood. Finally, PTH stimulates theabsorption of calcium from the foodin the gastrointestinal tract. Consistents central role in calcium meta-bolism, the release of this hormone isnot controlled by pituitary hormonesbut by the calcium levels in the blood.Thus, low calcium levels stimulate PTHrelease, whereas high calcium levelssuppress it.Many of the functions of PTH requireor are facilitated by a substance called1,25-dihydroxycholecalciferol, a deriva-tive of vitamin D. In addition, numerousother hormones are involved in regulat-s calcium levels and bonemetabolism, including estrogens, glu-cocorticoids, and growth hormone. (Formore information on the hormonalcontrol of bone and calcium metabolismsee the article by Sampson, pp. 190 The Pancreas and Its Hormones The pancreas is located in the abdomen,behind the stomach, and serves twodistinctly different functions. First, itacts as an exocrine organ, because themajority of pancreatic cells producevarious digestive enzymes that aresecreted into the gut and which areessential for the effective digestion offood. Second, the pancreas serves as anendocrine organ, because certain cellclusters (i.e., the Islets of Langerhans)produce two hormonesthat are released into theblood and play pivotal roles in bloodglucose regulation. Insulin Insulin is produced in the beta cells of theIslets of Langerhans. Its primary purpose 160 is to lower blood glucose levels; in fact,insulin is the only blood sugar-loweringhormone in the body. To this end, insulinpromotes the formation of storage formsof energy (e.g., glycogen, proteins, andlipids) and suppresses the breakdown ofthose stored nutrients. Accordingly, thetarget organs of insulin are primarily thosethat are specialized for energy storage, suchas the liver, muscles, and adipose tissue.Specifically, insulin has the followingPromotes glucose uptake into cellsand its conversion into glycogen,stimulates the breakdown of glucose,Stimulates the transport of aminoacids into cells and protein synthesisin muscle cells, thereby lowering thelevels of amino acids available forgluconeogenesis in the liverIncreases fat synthesis in the liverand adipose tis

sue, thereby lower-ing the levels of glycerol, whichalso can serve as a starting materialThe release of insulin is controlledby various factors, including bloodglucose levels; other islet hormones(e.g., glucagon); and, indirectly, otherlevels (e.g., GH, glucocorticoids, andthyroid hormone). Glucagon regulatingpancreatic hormone is glucagon, whichis produced in the alpha cells of the Isletsof Langerhans. Glucagon increases bloodglucose levels; accordingly, its main actionsgenerally are opposite to those of insulin.For example, glucagon increases glyco-gen breakdown and gluconeogenesis inthe liver as well as the breakdown of lipidsand proteins. The release of glucagon isregulated by many of the same factorss release, but sometimes withthe opposite effect. Thus, an increase inblood glucose levels stimulates insulinrelease but inhibits glucagon release.A finely tuned balance between the act-for maintaining blood sugar levels.Accordingly, disturbances of that balance,ity of the body to respond adequately toinsulin, result in serious disorders, such asdiabetes mellitus. (For more informationof diabetes, see the article by Emanueleand colleagues, pp. 211 Hormone Systems As this article has indicated in describ-ing the various endocrine glands andtheir hormones, some hormones arecontrolled directly by the metabolicpathways that they influence. Forexample, blood sugar levels directlycontrol insulin and glucagon releaseby the pancreas, and calcium levels in the blood regulate PTH release.Conversely, many hormones producedby target glands are regulated by pituitaryhormones, which in turn are controlledby hypothalamic hormones. Examplesof such regulatory hormonal cascadesinclude the hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-gonadal (HPG) axis, and thehypothalamic-pituitary-thyroidal (HPT)axis, which are described briefly in thefollowing sections (see figure 3, p.162). The HPA Axis Activation of the HPA axis, whichregulates various metabolic functions,is initiated with the release of CRHfrom the hypothalamus. This releaseoccurs in response to various stimuli,or psychological stress; during the nor-mal sleep-wake cycle; and in rto certain neurotransmitters. CRHthen stimulates the anterior pituitaryto produce ACTH. (In addition toCRH, AVP from the hypothalamusalso can stimulate ACTH release).ACTH, in turn, activates adrenalhormone production, primarily of cortisol, which mediates theThe activity of the HPA axis is regu-lated by negative feedback mechanisms.Thus, increased cortisol levels repressCRH release by the hypothalamusand ACTH release by the pituitary. Inaddition, ACTH can directly inhibithypothalamic CRH release.Any disturbances in the HPA axiscan result in serious medical conse-quences. For example, insufficienthormone production by the adrenalcortex causes Addisonis characterized by muscle weakness,dehydration, loss of appetite (i.e.,anorexia), nausea, vomiting, diarrhea,fever, abdominal pain, tiredness, andmalaise. Patients with this diseaseexhibit low levels of plasma cortisolbut high levels of ACTH. The increasein ACTH levels represents a vainattempt by the pituitary to stimulatehormone production in the unrespon-sive adrenal cortex. Equally deleteriousis the excessiveglucocorticoid production that resultsfrom excess ACTH release (i.e., Cushingsyndrome). Those patients experiencesymptoms such as muscle weaknessand wasting, back pain from osteoporo-sis,a tendency to bruise easily, redis-tribution of body fat (i.e., a rounded face, prominent abdomen,and thin legs)

, and various psycholog-ical disturbances. Because of the nega-tive feedback mechanism of the HPAs cortisol levels arehigh and the ACTH levels are low. Both acute and chronic alcohol consumption have been shown to acti-vate the HPA axis, and some drinkersdevelop a so-called pseudo-Cushingsyndrome that disappears with absti-nence (Veldman and Meinders 1996;Emanuele and Emanuele 1997). (Formore information on alcoholthe HPA axis and its relation to alcoholcraving, see the article by Gianoulakis,pp. 202 The HPG Axis In both men and women, the HPGaxis is the hormone system that controlsthe release of sex hormones. In bothgenders, the system is activated byGnRH, which is released regularly inshort bursts from the hypothalamus.GnRH then stimulates the release ofFSH and LH from the anterior pituitary. The Endocrine System 161 162 Figure 3 Schematic representation of the HPA, HPG, and HPT axes. For each system, the hypothalamus secretes releasing hormones (i.e., CRH, GnRH, and TRH) that act on the pituitary gland. In response to those stimuli, the pituitary glandand T4metabolism as well as feed back on the hypothalamus and pituitary. NOTE: = stimulates; = inhibits; ACTH = adrenocorticotropic hormone; CRH = corticotropin-releasing hormone; FSH = follicle-stimu GnRH HypothalamusMale HPG AxisHPT AxisHPA Axis + + + + Estrogen Progesterone Anterior Female HPG Axis Ovaries + + + / / + +pituitaryAdrenal glandKidney + + TSH Increasesmetabolism , T + + + 34 In men, LH stimulates certaincells in the testes (i.e., Leydig cells)to release testosterone. FSH andtestosterone are key regulators ofSertoli cells), which support andis regulated through a variety offactors. For example, testosterone is part of a negative feedbackmechanism that inhibits GnRHrelease by the hypothalamus and LH release by the pituitary. Inaddition, the Sertoli cells secrete aprevents FSH release from thepituitary. Finally, the Leydig cellsand, to a lesser extent, the Sertolicells produce a substance calledsecretion and thus has the oppositeIn women, during the menstrualcycle, LH and FSH stimulate theovarian follicle that contains thematuring egg to produce estradiol.After ovulation has occurred, LH also promotes production of proges-terone and estradiol by the corpusluteum. Both hormones participatein a negative feedback mechanismthrough most of the menstrual cycle,suppressing GnRH release from the hypothalamus and LH releasefrom the pituitary. Shortly beforeovulation, however, a positive feed-back mechanism is activated byLH release from the pituitary. Theresulting surge in LH levels ultimatelyleads to ovulation, the formation ofthe corpus luteum, and progesteronerelease. Progesterone exerts a negativefeedback on LH and FSH release, The Endocrine System 163 One of the essential hormonal systems regulating normalbody functioning is the hypothalamic-pituitary-thyroid(HPT) axis, which controls the metabolism of all cells. Ascertain conditions can modify the release of hormonesinvolved in this axis. In healthy nonalcoholics, alcoholchanges in the HPT axis (Emanuele and Emanuele1997). Conversely, some effects of alcohol on the HPTaxis have been observed in alcoholics. The effects differstudied. In alcoholics undergoing withdrawal, baselinelevels of thyroid hormone (i.e., Tdiffer only minimally from those in nonalcoholics. Theability of hypothalamic thyrotropin-releasing hormone(TRH) to activate the release of thyroid-stimulatinghormone (TSH) from the pituitary, however, is impairedin these alcoholics (Emanuele and Emanuele 1997). effec

t may result from alcoholon the neurotransmitter dopamine. Dopamine producedin the hypothalamus acts not only as a neurotransmitterbut also as a hormone in that it inhibits the release ofboth TSH and prolactin from the pituitary. Alcoholhas been shown to increase dopaminergic activity andthereby may suppress the TSH response to TRH. Thishypothesis is supported by the fact that prolactin releasein response to TRH also is blunted in alcoholics under-s effects on the HPT axis are even more com-plex in abstinent alcoholics (Garbutt et al. 1995). Inthose people, the baseline levels of Tare lower than in nonalcoholics. It is unclear, however,if this change represents a direct effect of long-term alcohol consumption or results from co-occurring alcohol-related illnesses, because thyroid hormone levels are often reduced in patients with acute or chronicnon-thyroidrelated illnesses, such as sepsis, burns, ormajor trauma. In addition to the reduced thyroid hormone levels, however, the TSH response to TRHremains blunted in abstinent alcoholics, whereas the pro-lactin response to TRH has returned to normal levels.This observation indicates that a factor other than dopa-mechanisms are unknown. Finally, some intriguing findings have suggested thatabnormal responses of the HPT axis may represent amarker for a personsome people who are at high risk for developing alcoholism,exhibit a blunted TSH response to TRH (Emanuele andEmanuele 1997). These observations still require furtherinvestigation, however, for researchers to fully understand ÑSusanne Hiller-Sturmhšfel and Andrzej BartkeReferences , M.A.The endocrine system: Alcohol Alcohol Health & Research World , G.A.Thyrotropin-releasing Drug and Alcohol AbuseReviews: Volume 6. Alcohol and Hormones . Totowa, NJ: Humana Press,Ð145. Alcohol Hypothalamic-Pituitary-Thyroid Axis causing LH levels to decline again. Inrelease from the pituitary is reguby inhibin, a substance producedbycertain cells in the ovarian follicle.Both acute and chronic alcohol con-sumption can interfere with the normalfunctioning of the HPG axis, resultingin reduced fertility or even infertility in both men and women and in men-strual disturbances in women. (For moreinformationon alcoholarticles by Dees and colleagues, pp. 165169, and by Emanuele and Emanuele,pp. 195 The HPT Axis axis control the metabolic processesof all cells in the body and are there-fore crucial for the organism to func-tionnormally. The secretion of TRHfrom the hypothalamus activates theHPT axis. After reaching the pitu-itary, TRH stimulates the release of TSH, which in turn promotes theproductionand release of Tby the thyroid gland. Negative feed-the hypothalamusand the pituitaryregulate the HPT system. (For asummaryof alcoholHPT axis, see sidebar, p. 163.) Summary The neuroendocrine system is ahighly complex and tightly controllednetwork of hormones released byendocrine glands throughout thebody. The levels of some of thehormones are regulated in a fairlystraightforward manner by the endproducts that they influence. Thus,blood sugar levels primarily regulateinsulin and glucagon release by thepancreas. Other hormones (e.g., thoseof the HPA, HPG, and HPT axes)are parts of hormone cascades whoseactivities are controlled throughelaborate feedback mechanisms. Inaddition, numerous indirect inter-actions exist between the varioushormone systems governing bodyfunctioning. For example, hormonessuch as GH and thyroid hormone,through their effects on cellular meta-els and, accordingly, insulin release.Similarly, alcoholhor

mone system may have indirectconsequences for other systems, therebyon the functioning of virtually everyorgan in the body. It is important tokeep this interconnectedness of neu-roendocrine systems in mind whens impact on varioushormones, which are described inthe remaining articles in this issue.  References C Basic Endocrinology for Students of Pharmacy and Amsterdam: HarwoodC.; LONGCOPE, C.; SAMPBELLAHLERelation of reported alcohol ingestion to plasma Cancer Causesand Control , M.A.The endocrine Alcohol Health & Research World , D.H.The associ-tionand serum estradiol and testosterone levels in Alcoholism: Clinical and ExperimentalResearch , V.Moderate alcohol consumption and Alcoholism: Clinical and Experimental Research , P.R.Effects of Journal of the National Cancer Institute , A.E.On the Endocrine Reviews 17:262Ð268, 1996.WRONENBERGH.M.; Williams Textbookof Endocrinology. 9th ed. Philadelphia: W.B.Saunders, 1998. 164 The Endocrine System An Overview Susanne Hiller-Sturmh A plethora of hormones regulate many of the bodyÕs functions, including growth anddevelopment, metabolism, electrolyte balances, and reproduction. Numerous glandsthroughout the body produce hormones. The hypothalamus produces several releasing andinhibiting hormones that act on the pituitary gland, stimulating the release of pituitaryhormones. Of the pituitary hormones, several act on other glands located in various regionsof the body, whereas other pituitary hormones directly affect their target organs. Otherhormone-producing glands throughout the body include the adrenal glands, which primarilyproduce cortisol; the gonads (i.e., ovaries and testes), which produce sex hormones; thethyroid, which produces thyroid hormone; the parathyroid, which produces parathyroidhormone; and the pancreas, which produces insulin and glucagon. Many of these hormonesare part of regulatory hormonal cascades involving a hypothalamic hormone, one or morepituitary hormones, and one or more target gland hormones. EYWORDS:endocrine function; Vol. 22, No. 3, 1998153 or the body to function properly,its various parts and organs mustensure that a constant internal environ-For example, neither the body temper-ature nor the levels of salts and minerals(i.e., electrolytes) in the blood mustfluctuate beyond preset limits. Com-munication among various regions ofthe organism to respond appropriatelyexternal environments. Two systemshelp ensure communication: the nervoussystem and the hormonal (i.e., neuroen-docrine) system. The nervous systemgenerally allows rapid transmissioninformation between different bodyregions. Conversely, hormonal commu-nication, which relies on the productionand release of hormones from variousglands and on the transport of thosehormones via the bloodstream, is bettersuited for situations that require morewidespread and longer lasting regulatorysystems complement each other. Inaddition, both systems interact: Stimulifrom the nervous system can influencethe release of certain hormones andvice versa.Generally speaking, hormones con-trolthe growth, development, andmetabolism of the body; the electrolytecomposition of bodily fluids; and repro-duction. This article provides anoverview of the hormone systemsinvolved in those regulatory processes.The article first summarizes some of thebody, then reviews the various glandsinvolved in those processes and the Sis a science editor of Alcohol Health &Research World ARTKE.D., is professorand chairman of physiology at SouthernIllinois University School of Medicine,Carbondale, I