56 - Welcome to MHHE

1125

56The Endocrine

System

Concept Outline

56.1 Regulation is often accomplished by chemicalmessengers.

Types of Regulatory Molecules. Regulatory moleculesmay function as neurotransmitters, hormones, or as organ-specific regulators.Endocrine Glands and Hormones. Endocrine glandssecrete molecules called hormones into the blood.Paracrine Regulation. Paracrine regulators act withinorgans that produce them.

56.2 Lipophilic and polar hormones regulate theirtarget cells by different means.

Hormones That Enter Cells. Steroid and thyroidhormones act by entering target cells and stimulatingspecific genes.Hormones That Do Not Enter Cells. All otherhormones bind to receptors on the cell surface and activatesecond-messenger molecules within the target cells.

56.3 The hypothalamus controls the secretions of thepituitary gland.

The Posterior Pituitary Gland. The posterior pituitaryreceives and releases hormones from the hypothalamus.The Anterior Pituitary Gland. The anterior pituitaryproduces a variety of hormones under stimulation fromhypothalamic releasing hormones.

56.4 Endocrine glands secrete hormones that regulatemany body functions.

The Thyroid and Parathyroid Glands. The thyroidhormones regulate metabolism; the parathyroid glandsregulate calcium balance.The Adrenal Glands. The adrenal medulla secretesepinephrine during the fight-or-flight reaction, while theadrenal cortex secretes steroid hormones that regulateglucose and mineral balance.The Pancreas. The islets of Langerhans in the pancreassecrete insulin, which acts to lower blood glucose, andglucagon, which acts to raise blood glucose.Other Endocrine Glands. The gonads, pineal gland,thymus, kidneys, and other organs secrete importanthormones that have a variety of functions.

The tissues and organs of the vertebrate body cooperateto maintain homeostasis of the body’s internal envi-

ronment and control other body functions such as repro-duction. Homeostasis is achieved through the actions ofmany regulatory mechanisms that involve all the organs ofthe body. Two systems, however, are devoted exclusively tothe regulation of the body organs: the nervous system andthe endocrine system (figure 56.1). Both release regulatorymolecules that control the body organs by first binding toreceptor proteins in the cells of those organs. In this chap-ter we will examine these regulatory molecules, the cellsand glands that produce them, and how they function toregulate the body’s activities.

FIGURE 56.1The endocrine system controls when animals breed. TheseJapanese macaques live in a close-knit community whosemembers cooperate to ensure successful breeding and raising ofoffspring. Not everybody breeds at the same time becausehormone levels vary among individuals.

times called a neurohormone. The distinction betweenthe nervous system and endocrine system blurs when itcomes to such molecules. Indeed, because some neurons inthe brain secrete hormones, the brain can be considered anendocrine gland!

In addition to the chemical messengers released asneurotransmitters and as hormones, other chemical regu-latory molecules are released and act within an organ. Inthis way, the cells of an organ regulate one another. Thistype of regulation is not endocrine, because the regula-tory molecules work without being transported by theblood, but is otherwise similar to the way that hormonesregulate their target cells. Such regulation is calledparacrine. Another type of chemical messenger that isreleased into the environment is called a pheromone.These messengers aid in the communication between an-imals, not in the regulation within an animal. A compari-son of the different types of chemical messengers usedfor regulation is given in figure 56.2.

Regulatory molecules released by axons at a synapse areneurotransmitters, those released by endocrine glandsinto the blood are hormones, and those that act withinthe organ in which they are produced are paracrineregulators.

1126 Part XIV Regulating the Animal Body

Types of Regulatory MoleculesAs we discussed in chapter 54, the axons of neurons secretechemical messengers called neurotransmitters into thesynaptic cleft. These chemicals diffuse only a short distanceto the postsynaptic membrane, where they bind to their re-ceptor proteins and stimulate the postsynaptic cell (anotherneuron, or a muscle or gland cell). Synaptic transmissiongenerally affects only the one postsynaptic cell that receivesthe neurotransmitter.

A hormone is a regulatory chemical that is secreted intothe blood by an endocrine gland or an organ of the bodyexhibiting an endocrine function. The blood carries thehormone to every cell in the body, but only the targetcells for a given hormone can respond to it. Thus, the dif-ference between a neurotransmitter and a hormone is notin the chemical nature of the regulatory molecule, butrather in the way it is transported to its target cells, and itsdistance from these target cells. A chemical regulator callednorepinephrine, for example, is released as a neurotrans-mitter by sympathetic nerve endings and is also secreted bythe adrenal gland as a hormone.

Some specialized neurons secrete chemical messengersinto the blood rather than into a narrow synaptic cleft. Inthese cases, the chemical that the neurons secrete is some-

56.1 Regulation is often accomplished by chemical messengers.

AxonNeurotransmitter

Endocrine gland

Target cell

Paracrine regulator

Receptor proteins

Hormonecarried by blood

FIGURE 56.2The functions of organs are influenced by neural, paracrine, and endocrine regulators. Each type of chemical regulator binds in aspecific fashion to receptor proteins on the surface of or within the cells of target organs.

Endocrine Glands and HormonesThe endocrine system (figure 56.3) includes all of the or-gans that function exclusively as endocrine glands—suchas the thyroid gland, pituitary gland, adrenal glands, andso on (table 56.1)—as well as organs that secrete hor-mones in addition to other functions. Endocrine glandslack ducts and thus must secrete into surrounding bloodcapillaries, unlike exocrine glands, which secrete theirproducts into a duct.

Hormones secreted by endocrine glands belong to fourdifferent chemical categories:

1. Polypeptides. These hormones are composed ofchains of amino acids that are shorter than about100 amino acids. Some important examples includeinsulin and antidiuretic hormone (ADH).

2. Glycoproteins. These are composed of a polypep-tide significantly longer than 100 amino acids towhich is attached a carbohydrate. Examples includefollicle-stimulating hormone (FSH) and luteinizinghormone (LH).

3. Amines. Derived from the amino acids tyrosine andtryptophan, they include hormones secreted by theadrenal medulla, thyroid, and pineal glands.

4. Steroids. These hormones are lipids derived fromcholesterol, and include the hormones testosterone,estradiol, progesterone, and cortisol.

Steroid hormones can be subdivided into sex steroids,secreted by the testes, ovaries, placenta, and adrenal cortex,and corticosteroids, secreted only by the adrenal cortex(the outer portion of the adrenal gland). The corticos-teroids include cortisol, which regulates glucose balance,and aldosterone, which regulates salt balance.

The amine hormones secreted by the adrenal medulla(the inner portion of the adrenal gland), known as cate-cholamines, include epinephrine (adrenaline) and norepi-nephrine (noradrenaline). These are derived from theamino acid tyrosine. Another hormone derived from tyro-sine is thyroxine, secreted by the thyroid gland. The pinealgland secretes a different amine hormone, melatonin, de-rived from tryptophan.

All hormones may be categorized as lipophilic (fat-soluble) or hydrophilic (water-soluble). The lipophilichormones include the steroid hormones and thyroxine; allother hormones are water-soluble. This distinction is im-portant in understanding how these hormones regulatetheir target cells.

Neural and Endocrine Interactions

The endocrine system is an extremely important regulatorysystem in its own right, but it also interacts and cooperateswith the nervous system to regulate the activities of theother organ systems of the body. The secretory activity ofmany endocrine glands is controlled by the nervous system.Among such glands are the adrenal medulla, posterior pitu-

itary, and pineal gland. These three glands are derivedfrom the neural ectoderm (to be discussed in chapter 60),the same embryonic tissue layer that forms the nervous sys-tem. The major site for neural regulation of the endocrinesystem, however, is the brain’s regulation of the anteriorpituitary gland. As we’ll see, the hypothalamus controls thehormonal secretions of the anterior pituitary, which in turnregulates other endocrine glands. On the other hand, thesecretion of a number of hormones is largely independentof neural control. The release of insulin by the pancreasand aldosterone by the adrenal cortex, for example, arestimulated primarily by increases in the blood concentra-tions of glucose and potassium (K+), respectively.

Any organ that secretes a hormone from a ductlessgland is part of the endocrine system. Hormones maybe any of a variety of different chemicals.

Chapter 56 The Endocrine System 1127

Parathyroid glands(behind thyroid)

Thymus

Adrenalglands

Ovaries(in females)

Testes(in males)

Pancreas

Thyroidgland

Pituitarygland

Pinealgland

FIGURE 56.3The human endocrine system. The major endocrine glands areshown, but many other organs secrete hormones in addition totheir primary functions.

Paracrine RegulationParacrine regulation occurs in many organs and among thecells of the immune system. Some of these regulatory mol-ecules are known as cytokines, particularly if they regulatedifferent cells of the immune system. Other paracrine regu-lators are called growth factors, because they promotegrowth and cell division in specific organs. Examples in-clude platelet-derived growth factor, epidermal growth factor,and the insulin-like growth factors that stimulate cell divisionand proliferation of their target cells. Nerve growth factor isa regulatory molecule that belongs to a family of paracrineregulators of the nervous system called neurotrophins.

Nitric oxide, which can function as a neurotransmitter (seechapter 54), is also produced by the endothelium of bloodvessels. In this context, it is a paracrine regulator because itdiffuses to the smooth muscle layer of the blood vessel andpromotes vasodilation. The endothelium of blood vessels also

produces other paracrine regulators, including endothelin,which stimulates vasoconstriction, and bradykinin, which pro-motes vasodilation. This paracrine regulation supplementsthe regulation of blood vessels by autonomic nerves.

The most diverse group of paracrine regulators are theprostaglandins. A prostaglandin is a 20-carbon-long fattyacid that contains a five-member carbon ring. This mole-cule is derived from the precursor molecule arachidonic acid,released from phospholipids in the cell membrane underhormonal or other stimulation. Prostaglandins are pro-duced in almost every organ and participate in a variety ofregulatory functions, including:

1. Immune system. Prostaglandins promote many as-pects of inflammation, including pain and fever.Drugs that inhibit prostaglandin synthesis help to al-leviate these symptoms.

2. Reproductive system. Prostaglandins may play a


Table 56.1 Principal Endocrine Glands and Their Hormones*

Endocrine Gland Target Chemicaland Hormone Tissue Principal Actions Nature

POSTERIOR LOBE OF PITUITARYAntidiuretic hormone (ADH)

Oxytocin

ANTERIOR LOBE OF PITUITARYGrowth hormone (GH)

Adrenocorticotropic hormone (ACTH)Thyroid-stimulating hormone (TSH)Luteinizing hormone (LH)

Follicle-stimulating hormone (FSH)Prolactin (PRL)Melanocyte-stimulating hormone (MSH)

THYROID GLANDThyroxine (thyroid hormone)

Calcitonin

PARATHYROID GLANDSParathyroid hormone

Kidneys

UterusMammary glands

Many organs

Adrenal cortex

Thyroid gland

Gonads

Gonads

Mammary glandsSkin

Most cells

Bone

Bone, kidneys,digestive tract

Stimulates reabsorption of water; conserves water

Stimulates contractionStimulates milk ejection

Stimulates growth by promoting protein synthesis and fat breakdownStimulates secretion of adrenal cortical hormones such as cortisolStimulates thyroxine secretion

Stimulates ovulation and corpus luteum formation infemales; stimulates secretion of testosterone in malesStimulates spermatogenesis in males; stimulatesdevelopment of ovarian follicles in femalesStimulates milk productionStimulates color change in reptiles and amphibians;unknown function in mammals

Stimulates metabolic rate; essential to normal growth and developmentLowers blood calcium level by inhibiting loss of calcium from bone

Raises blood calcium level by stimulating bone breakdown; stimulates calcium reabsorption in kidneys; activates vitamin D

Peptide (9 amino acids)Peptide (9 amino acids)

Protein

Peptide (39 amino acids)Glycoprotein

Glycoprotein

Glycoprotein

ProteinPeptide (twoforms; 13 and 22amino acids)

Iodinated aminoacidPeptide (32 amino acids)

Peptide (34 amino acids)

*These are hormones released from endocrine glands. As discussed previously, many hormones are released from other body organs.

role in ovulation. Excessive prostaglandin productionmay be involved in premature labor, endometriosis,or dysmenorrhea (painful menstrual cramps).

3. Digestive system. Prostaglandins produced by thestomach and intestines may inhibit gastric secretionsand influence intestinal motility and fluid absorption.

4. Respiratory system. Some prostaglandins causeconstriction, whereas others cause dilation of bloodvessels in the lungs and of bronchiolar smooth muscle.

5. Circulatory system. Prostaglandins are needed forproper function of blood platelets in the process ofblood clotting.

6. Urinary system. Prostaglandins produced in therenal medulla cause vasodilation, resulting in increasedrenal blood flow and increased excretion of urine.

The synthesis of prostaglandins are inhibited by aspirin.Aspirin is the most widely used of the nonsteroidal anti-

inflammatory drugs (NSAIDs), a class of drugs that also in-cludes indomethacin and ibuprofen. These drugs producetheir effects because they specifically inhibit the enzymecyclooxygenase-2 (cox-2), needed to produce prostaglandinsfrom arachidonic acid. Through this action, the NSAIDsinhibit inflammation and associated pain. Unfortunately,NSAIDs also inhibit another similar enzyme, cox-1, whichhelps maintain the wall of the digestive tract, and in sodoing can produce severe unwanted side effects, includinggastric bleeding and prolonged clotting time. A new kind ofpain reliever, celecoxib (Celebrex), inhibits cox-2 but notcox-1, a potentially great benefit to arthritis sufferers andothers who must use pain relievers regularly.

The neural and endocrine control systems aresupplemented by paracrine regulators, including theprostaglandins, which perform many diverse functions.


ADRENAL MEDULLAEpinephrine (adrenaline) and norepinephrine (noradrenaline)

ADRENAL CORTEXAldosteroneCortisol

PANCREASInsulin

Glucagon

OVARYEstradiol

Progesterone

TESTISTestosterone

PINEAL GLANDMelatonin

Table 56.1 Principal Endocrine Glands and Their Hormones

Endocrine Gland Target Chemicaland Hormone Tissue Principal Actions Nature

Smooth muscle, cardiac muscle, blood vessels

Kidney tubulesMany organs

Liver, skeletal muscles, adipose tissueLiver, adipose tissue

General

Female reproductive structuresUterusMammary glands

Many organs

Male reproductive structures

Gonads, pigment cells

Initiate stress responses; raise heart rate, blood pressure, metabolic rate; dilate blood vessels;mobilize fat; raise blood glucose level

Maintains proper balance of Na+ and K+ ionsAdaptation to long-term stress; raises blood glucoselevel; mobilizes fat

Lowers blood glucose level; stimulates storage ofglycogen in liver

Raises blood glucose level; stimulates breakdown ofglycogen in liver

Stimulates development of secondary sexcharacteristics in femalesStimulates growth of sex organs at puberty andmonthly preparation of uterus for pregnancyCompletes preparation for pregnancyStimulates development

Stimulates development of secondary sexcharacteristics in males and growth spurt at pubertyStimulates development of sex organs; stimulatesspermatogenesis

Function not well understood; influencespigmentation in some vertebrates; may controlbiorhythms in some animals; may influence onset of puberty in humans

Amino acidderivatives

SteroidSteroid



Steroid

Steroid

Steroid

Amino acidderivative

Hormones That Enter CellsAs we mentioned previously, hormones can be dividedinto those that are lipophilic (lipid-soluble) and thosethat are hydrophilic (water-soluble). The lipophilichormones—all of the steroid hormones (figure 56.4) andthyroxine—as well as other lipophilic regulatory mole-cules (including the retinoids, or vitamin A) can easilyenter cells. This is because the lipid portion of the cellmembrane does not present a barrier to the entry oflipophilic regulators. Therefore, all lipophilic regulatorymolecules have a similar mechanism of action. Water-soluble hormones, in contrast, cannot pass through cellmembranes. They must regulate their target cellsthrough different mechanisms.

Steroid hormones are lipids themselves and thuslipophilic; thyroxine is lipophilic because it is derivedfrom a nonpolar amino acid. Because these hormones arenot water-soluble, they don’t dissolve in plasma but rathertravel in the blood attached to protein carriers. When thehormones arrive at their target cells, they dissociate fromtheir carriers and pass through the plasma membrane of


56.2 Lipophilic and polar hormones regulate their target cells by different means.

CH3CH3

CH3

HOEstradiol - 17�

OH

Testosterone

CH3

O

O

OHCH3

Cortisol (hydrocortisone)

HO

C O

OH

CH2OH

FIGURE 56.4Chemical structures of somesteroid hormones. Steroidhormones are derived from theblood lipid cholesterol. Thehormones shown, cortisol,estradiol, and testosterone,differ only slightly in chemicalstructure yet have widelydifferent effects on the body.Steroid hormones are secretedby the adrenal cortex, testes,ovaries, and placenta.

Nucleus

Cytoplasm

1

1 Steroid hormone (S) passes through plasma membrane.

2

2

Inside target cell, the steroid hormone binds to a specific receptor protein in the cytoplasm or nucleus.

3

3

Hormone-receptor complex enters the nucleus and binds to DNA, causing gene transcription.

5

5

Protein is produced.

4

4

Protein synthesis is induced.

Plasma membrane

ChromosomemRNA

Protein

Steroidhormone

Blood plasma

Interstitialfluid

S

S

S

S

Proteincarrier

FIGURE 56.5The mechanism of steroid hormone action. Steroid hormones are lipid-soluble and thus readily diffuse through the plasma membraneof cells. They bind to receptor proteins in either the cytoplasm or nucleus (not shown). If the steroid binds to a receptor in the cytoplasm,the hormone-receptor complex moves into the nucleus. The hormone-receptor complex then binds to specific regions of the DNA,stimulating the production of messenger RNA (mRNA).

the cell (figure 56.5). Some steroid hormones then bind tovery specific receptor proteins in the cytoplasm, and thenmove as a hormone-receptor complex into the nucleus.Other steroids travel directly into the nucleus before en-countering their receptor proteins. Whether the steroidfinds its receptor in the nucleus or translocates with its re-ceptor to the nucleus from the cytoplasm, the rest of thestory is the same.

The hormone receptor, activated by binding to thelipophilic hormone, is now also able to bind to specific re-gions of the DNA. These DNA regions are known as thehormone response elements. The binding of the hormone-receptor complex has a direct effect on the level of tran-scription at that site by activating genetic transcription.This produces messenger RNA (mRNA), which then codesfor the production of specific proteins. These proteinsoften have enzymatic activity that changes the metabolismof the target cell in a specific fashion.

The thyroid hormone’s mechanism of action resemblesthat of the steroid hormones. Thyroxine contains fouriodines and so is often abbreviated T4 (for tetraiodothyro-nine). The thyroid gland also secretes smaller amounts of asimilar molecule that has only three iodines, called tri-iodothyronine (and abbreviated T3). Both hormones entertarget cells, but all of the T4 that enters is changed into T3(figure 56.6). Thus, only the T3 form of the hormone entersthe nucleus and binds to nuclear receptor proteins. Thehormone-receptor complex, in turn, binds to the appropri-ate hormone response elements on DNA.

The lipophilic hormones pass through the target cell’splasma membrane and bind to intracellular receptorproteins. The hormone-receptor complex then binds tospecific regions of DNA, thereby activating genes andregulating the target cells.


Nucleus

CytoplasmTriiodothyronine

Plasma membrane

mRNA

Receptorprotein

T4

T4

T3

T3

T3

T4

Proteincarrier

Thyroxine

Blood plasma

Interstitialfluid

FIGURE 56.6The mechanism of thyroxine action. Thyroxine contains four iodines. When it enters the target cell, thyroxine is changed intotriiodothyronine, with three iodines. This hormone moves into the nucleus and binds to nuclear receptors. The hormone-receptorcomplex then binds to regions of the DNA and stimulates gene transcription.

Hormones That Do Not Enter CellsHormones that are too large or too polar to cross theplasma membranes of their target cells include all of thepeptide and glycoprotein hormones, as well as the cate-cholamine hormones epinephrine and norepinephrine.These hormones bind to receptor proteins located on theouter surface of the plasma membrane—the hormones donot enter the cell. If you think of the hormone as a messen-ger sent from an endocrine gland to the target cell, it is evi-dent that a second messenger is needed within the targetcell to produce the effects of the hormone. A number ofdifferent molecules in the cell can serve as second messen-gers, as we saw in chapter 7. The interaction between thehormone and its receptor activates mechanisms in theplasma membrane that increase the concentration of thesecond messengers within the target cell cytoplasm.

The binding of a water-soluble hormone to its receptoris reversible and usually very brief. After the hormonebinds to its receptor and activates a second-messenger sys-tem, it dissociates from the receptor and may travel in theblood to another target cell somewhere else in the body.Eventually, enzymes (primarily in the liver) degrade thehormone by converting it into inactive derivatives.

The Cyclic AMP Second-Messenger System

The action of the hormone epinephrine can serve as an ex-ample of a second-messenger system. Epinephrine can bindto two categories of receptors, called alpha (α)- and beta (β)-adrenergic receptors. The interaction of epinephrine witheach type of receptor activates a different second-messengersystem in the target cell.

In the early 1960s, Earl Sutherland showed that cyclicadenosine monophosphate, or cyclic AMP (cAMP),serves as a second messenger when epinephrine binds toβ-adrenergic receptors on the plasma membranes of livercells (figure 56.7). The cAMP second-messenger systemwas the first such system to be described.

The β-adrenergic receptors are associated with mem-brane proteins called G proteins (see chapters 7 and 54).Each G protein is composed of three subunits, and thebinding of epinephrine to its receptor causes one of the Gprotein subunits to dissociate from the other two. Thissubunit then diffuses within the plasma membrane until itencounters adenylyl cyclase, a membrane enzyme that isinactive until it binds to the G protein subunit. When ac-tivated by the G protein subunit, adenylyl cyclase cat-alyzes the formation of cAMP from ATP. The cAMPformed at the inner surface of the plasma membrane dif-fuses within the cytoplasm, where it binds to and activatesprotein kinase-A, an enzyme that adds phosphate groupsto specific cellular proteins.

The identities of the proteins that are phosphorylated byprotein kinase-A varies from one cell type to the next, andthis variation is one of the reasons epinephrine has such di-

verse effects on different tissues. In liver cells, protein kinase-A phosphorylates and thereby activates another enzyme,phosphorylase, which converts glycogen into glucose.Through this multistep mechanism, epinephrine causes theliver to secrete glucose into the blood during the fight-or-flight reaction, when the adrenal medulla is stimulated by thesympathetic division of the autonomic nervous system (seechapter 54). In cardiac muscle cells, protein kinase-A phos-phorylates a different set of cellular proteins, which cause theheart to beat faster and more forcefully.

The IP3/Ca++ Second-Messenger System

When epinephrine binds to α-adrenergic receptors, itdoesn’t activate adenylyl cyclase and cause the productionof cAMP. Instead, through a different type of G protein, itactivates another membrane-bound enzyme, phospholipaseC (figure 56.8). This enzyme cleaves certain membranephospholipids to produce the second messenger, inositol


1

3

4

2

GTP

Activatesprotein

kinase-A

Activatesphosphorylase

G protein

Receptorprotein

Liver cell

Adenylylcyclase

cAMP

Glucose

Epinephrine

ATP

Glycogen

FIGURE 56.7The action of epinephrine on a liver cell. (1) Epinephrinebinds to specific receptor proteins on the cell surface. (2) Actingthrough intermediary G proteins, the hormone-bound receptoractivates the enzyme adenylyl cyclase, which converts ATP intocyclic AMP (cAMP). (3) Cyclic AMP performs as a secondmessenger and activates protein kinase-A, an enzyme that waspreviously present in an inactive form. (4) Protein kinase-Aphosphorylates and thereby activates the enzyme phosphorylase,which catalyzes the hydrolysis of glycogen into glucose.

trisphosphate (IP3). IP3 diffuses into the cytoplasm fromthe plasma membrane and binds to receptors located on thesurface of the endoplasmic reticulum.

Recall from chapter 5 that the endoplasmic reticulumis a system of membranous sacs and tubes that serves avariety of functions in different cells. One of its functionsis to accumulate Ca++ by actively transporting Ca++ out ofthe cytoplasm. Other pumps transport Ca++ from the cy-toplasm through the plasma membrane to the extracellu-lar fluid. These two mechanisms keep the concentrationof Ca++ in the cytoplasm very low. Consequently, there isan extremely steep concentration gradient for Ca++ be-tween the cytoplasm and the inside of the endoplasmicreticulum, and between the cytoplasm and the extracellu-lar fluid.

When IP3 binds to its receptors on the endoplasmicreticulum, it stimulates the endoplasmic reticulum to re-lease its stored Ca++. Calcium channels in the plasmamembrane may also open, allowing Ca++ to diffuse intothe cell from the extracellular fluid. Some of the Ca++ thathas suddenly entered the cytoplasm then binds to a pro-tein called calmodulin, which has regulatory functionsanalogous to those of cyclic AMP. One of the actions ofcalmodulin is to activate another type of protein kinase,resulting in the phosphorylation of a different set of cellu-lar proteins.

What is the advantage of having multiple second-messenger systems? Consider the antagonistic actions of ep-inephrine and insulin on liver cells. Epinephrine uses cAMPas a second messenger to promote the hydrolysis of glyco-gen to glucose, while insulin stimulates the synthesis ofglycogen from glucose. Clearly, insulin cannot use cAMP asa second messenger. Although the exact mechanism of in-

sulin’s action is still not well understood, insulin may act inpart through the IP3/Ca++ second-messenger system.

Not all large polar hormones act by increasing the con-centration of a second messenger in the cytoplasm of thetarget cell. Others cause a change in the shape of a mem-brane protein called an ion channel (see chapters 6 and 54).If these channels are normally “closed,” then a change inshape will open them allowing a particular ion to enter orleave the cell depending on its concentration gradient. If anion channel is normally open, a chemical messenger cancause it to close. For example, some hormones open Ca++

channels on smooth muscle cell membranes; other hor-mones close them. This will increase or decrease, respec-tively, the amount of muscle contraction.

The molecular mechanism for changing the shape of anion channel is similar to that for activating a second mes-senger. The hormone first binds to a receptor protein onthe outer surface of the target cell. This receptor proteinmay then use a G protein to signal the ion channel tochange shape.

Although G proteins play a major role in many hormonefunctions they don’t seem to be necessary for all identifiedactions of hormones on target cells. In the cases where Gproteins are not involved, the receptor protein is connecteddirectly to the enzyme or ion channel.

The water-soluble hormones cannot pass through theplasma membrane; they must rely on secondmessengers within the target cells to mediate theiractions. Such second messengers include cyclic AMP(cAMP), inositol trisphosphate (IP3), and Ca++. In manycases, the second messengers activate previouslyinactive enzymes.


G proteinEndoplasmicreticulum

Receptorprotein

Plasmamembrane

Phospholipase C

Ca++

Hormoneeffects

Calmodulin

IP3

1

4

56

Epinephrine

2

4

3

FIGURE 56.8The IP3/Ca++ second-messengersystem. (1) The hormone epinephrinebinds to specific receptor proteins onthe cell surface. (2) Acting through Gproteins, the hormone-bound receptoractivates the enzyme phospholipase C,which converts membranephospholipids into inositoltrisphosphate (IP3). (3) IP3 diffusesthrough the cytoplasm and binds toreceptors on the endoplasmicreticulum. (4) The binding of IP3 to itsreceptors stimulates the endoplasmicreticulum to release Ca++ into thecytoplasm. (5) Some of the releasedCa++ binds to a regulatory protein calledcalmodulin. (6) The Ca++/calmodulincomplex activates other intracellularproteins, ultimately producing theeffects of the hormone.

The Posterior Pituitary Gland The pituitary gland hangs by a stalk from the hypothala-mus of the brain (figure 56.9) posterior to the optic chiasm(see chapter 54). A microscopic view reveals that the glandconsists of two parts. The anterior portion appears glandu-lar and is called the anterior pituitary; the posterior por-tion appears fibrous and is the posterior pituitary. Thesetwo portions of the pituitary gland have different embry-onic origins, secrete different hormones, and are regulatedby different control systems.

The Posterior Pituitary Gland

The posterior pituitary appears fibrous because it containsaxons that originate in cell bodies within the hypothalamusand extend along the stalk of the pituitary as a tract of

fibers. This anatomical relationship results from the waythat the posterior pituitary is formed in embryonic devel-opment. As the floor of the third ventricle of the brainforms the hypothalamus, part of this neural tissue growsdownward to produce the posterior pituitary. The hypo-thalamus and posterior pituitary thus remain intercon-nected by a tract of axons.

The endocrine role of the posterior pituitary gland firstbecame evident in 1912, when a remarkable medical casewas reported: a man who had been shot in the head devel-oped the need to urinate every 30 minutes or so, 24 hours aday. The bullet had lodged in his pituitary gland. Subse-quent research demonstrated that removal of this glandproduces the same symptoms. Pituitary extracts were foundto contain a substance that makes the kidneys conservewater, and in the early 1950s investigators isolated a pep-tide from the posterior pituitary, antidiuretic hormone


56.3 The hypothalamus controls the secretions of the pituitary gland.

FIGURE 56.9The pituitary gland hangs by a short stalk from the hypothalamus. The pituitary gland (the oval structure hanging from the stalk),shown here enlarged 15 times, regulates hormone production in many of the body’s endocrine glands.

(ADH, also known as vasopressin), that stimulates waterretention by the kidneys (figure 56.10). When ADH ismissing, the kidneys do not retain water and excessivequantities of urine are produced. This is why the consump-tion of alcohol, which inhibits ADH secretion, leads to fre-quent urination.

The posterior pituitary also secretes oxytocin, a secondpeptide hormone which, like ADH, is composed of nineamino acids. Oxytocin stimulates the milk-ejection reflex,so that contraction of the smooth muscles around themammary glands and ducts causes milk to be ejected fromthe ducts through the nipple. During suckling, sensory re-ceptors in the nipples send impulses to the hypothalamus,which triggers the release of oxytocin. Oxytocin is alsoneeded to stimulate uterine contractions in women duringchildbirth. Oxytocin secretion continues after childbirth ina woman who is breast-feeding, which is why the uterus ofa nursing mother returns to its normal size after pregnancymore quickly than does the uterus of a mother who doesnot breast-feed.

ADH and oxytocin are actually produced by neuron cellbodies located in the hypothalamus. These two hormones aretransported along the axon tract that runs from the hypothal-amus to the posterior pituitary and are stored in the posteriorpituitary. In response to the appropriate stimulation—increased blood plasma osmolarity in the case of ADH, thesuckling of a baby in the case of oxytocin—the hormonesare released by the posterior pituitary into the blood. Be-cause this reflex control involves both the nervous and en-docrine systems, the secretion of ADH and oxytocin areneuroendocrine reflexes.

The posterior pituitary gland contains axons originatingfrom neurons in the hypothalamus. These neuronsproduce ADH and oxytocin, which are stored in andreleased from the posterior pituitary gland in responseto neural stimulation from the hypothalamus.


ADH

Dehydration Lowers blood volumeand pressure

Increased waterretention

Negativefeedback

Negativefeedback

Increasedvasoconstriction(in some vertebrates)leading to higherblood pressure

Reducedurine volume

Osmoreceptors

Osmoticconcentrationof bloodincreases

ADH synthesizedby neurosecretorycells in hypothalamus

ADH released from posteriorpituitary into blood

– –

FIGURE 56.10The effects of antidiuretichormone (ADH). An increase inthe osmotic concentration of theblood stimulates the posteriorpituitary gland to secrete ADH,which promotes water retention bythe kidneys. This works as anegative feedback loop to correctthe initial disturbance ofhomeostasis.

The Anterior Pituitary GlandThe anterior pituitary, unlike the posterior pituitary, doesnot develop from a downgrowth of the brain; instead, it de-velops from a pouch of epithelial tissue that pinches offfrom the roof of the embryo’s mouth. Because it is epithe-lial tissue, the anterior pituitary is a complete gland—itproduces the hormones it secretes. Many, but not all, ofthese hormones stimulate growth in their target organs, in-cluding other endocrine glands. Therefore, the hormonesof the anterior pituitary gland are collectively termed tropichormones (Greek trophe, “nourishment”), or tropins. Whenthe target organ of a tropic hormone is another endocrinegland, that gland is stimulated by the tropic hormone to se-crete its own hormones.

The hormones produced and secreted by different celltypes in the anterior pituitary gland (figure 56.11) includethe following:

1. Growth hormone (GH, or somatotropin) stimulatesthe growth of muscle, bone (indirectly), and other tis-sues and is also essential for proper metabolic regula-tion.

2. Adrenocorticotropic hormone (ACTH, or corti-cotropin) stimulates the adrenal cortex to produce cor-ticosteroid hormones, including cortisol (in humans)and corticosterone (in many other vertebrates), whichregulate glucose homeostasis.

3. Thyroid-stimulating hormone (TSH, or thy-rotropin) stimulates the thyroid gland to produce thy-roxine, which in turn stimulates oxidative respiration.

4. Luteinizing hormone (LH) is needed for ovulationand the formation of a corpus luteum in the femalemenstrual cycle (see chapter 59). It also stimulates thetestes to produce testosterone, which is needed forsperm production and for the development of malesecondary sexual characteristics.


Thyroid gland

Hypothalamus

Anteriorpituitary

Gonadotropic hormones:Follicle-stimulatinghormone (FSH) andluteinizing hormone (LH)

Mammary glandsin mammals

Musclesof uterus

Kidneytubules

Posteriorpituitary

Thyroid-stimulating hormone(TSH) Antidiuretic hormone

(ADH)

Adrenocorticotropic

hormone (ACTH)

Gro

wth

hor

mon

e (G

H)

Prolactin (PRL)

Oxytocin

Adrenalcortex

Boneand muscle

TestisOvary

Melanocytein amphibian

Melanocyte-stimulating hormone (MSH)

FIGURE 56.11The major hormones of the anterior and posterior pituitary glands. Only a few of the actions of these hormones are shown.

5. Follicle-stimulating hormone (FSH) is required forthe development of ovarian follicles in females. Inmales, it is required for the development of sperm.FSH and LH are both referred to as gonadotropins.

6. Prolactin (PRL) stimulates the mammary glands toproduce milk in mammals. It also helps regulate kid-ney function in vertebrates, the production of “cropmilk” (nutritional fluid fed to chicks by regurgita-tion) in some birds, and acts on the gills of fish thattravel from salt to fresh water to promote sodiumretention.

7. Melanocyte-stimulating hormone (MSH) stimu-lates the synthesis and dispersion of melanin pigment,which darken the epidermis of some fish, amphibians,and reptiles. MSH has no known specific function inmammals, but abnormally high amounts of ACTHcan cause skin darkening because it contains theamino acid sequence of MSH within its structure.

Growth Hormone

The importance of the anterior pituitary gland first be-came understood in 1909, when a 38-year-old SouthDakota farmer was cured of the growth disorderacromegaly by the surgical removal of a pituitary tumor.Acromegaly is a form of gigantism in which the jaw beginsto protrude and other facial features thicken. It was discov-ered that gigantism is almost always associated with pitu-itary tumors. Robert Wadlow, born in 1928 in Alton, Illi-nois, stood 8 feet, 11 inches tall and weighed 485 poundsbefore he died from infection at age 22 (figure 56.12). Hewas the tallest human being ever recorded, and he was stillgrowing the year he died.

We now know that gigantism is caused by the excessivesecretion of growth hormone (GH) by the anterior pitu-itary gland in a growing child. GH stimulates protein syn-thesis and growth of muscles and connective tissues; it alsoindirectly promotes the elongation of bones by stimulatingcell division in the cartilaginous epiphyseal growth plates ofbones. Researchers found that this stimulation does notoccur in the absence of blood plasma, suggesting that bonecells lack receptors for GH and that the stimulation by GHwas indirect. We now know that GH stimulates the pro-duction of insulin-like growth factors, which are pro-duced by the liver and secreted into the blood in responseto stimulation by GH. The insulin-like growth factors thenstimulate growth of the epiphyseal growth plates and thuselongation of the bones.

When a person’s skeletal growth plates have convertedfrom cartilage into bone, however, GH can no longer causean increase in height. Therefore, excessive GH secretion inan adult produces bone and soft tissue deformities in thecondition called acromegaly. A deficiency in GH secretionduring childhood results in pituitary dwarfism, a failure toachieve normal growth.

Other Anterior Pituitary Hormones

Prolactin is like growth hormone in that it acts on organsthat are not endocrine glands. In addition to its stimulationof milk production in mammals and “crop milk” produc-tion in birds, prolactin has varied effects on electrolyte bal-ance by acting on the kidneys, the gills of fish, and the saltglands of marine birds (discussed in chapter 58). Unlikegrowth hormone and prolactin, the other anterior pituitaryhormones act on specific glands.

Some of the anterior pituitary hormones that act on spe-cific glands have common names, such as thyroid-stimulatinghormone (TSH), and alternative names that emphasize thetropic nature of the hormone, such as thyrotropin. TSHstimulates only the thyroid gland, and adrenocorticotropichormone (ACTH) stimulates only the adrenal cortex (outerportion of the adrenal glands). Follicle-stimulating hor-mone (FSH) and luteinizing hormone (LH) act only on thegonads (testes and ovaries); hence, they are collectivelycalled gonadotropic hormones. Although both FSH and LHact on the gonads, they each act on different target cells inthe gonads of both females and males.


FIGURE 56.12The Alton giant. This photograph of Robert Wadlow of Alton,Illinois, taken on his 21st birthday, shows him at home with hisfather and mother and four siblings. Born normal size, hedeveloped a growth hormone–secreting pituitary tumor as ayoung child and never stopped growing during his 22 years of life.

Hypothalamic Control of Anterior PituitaryGland Secretion

The anterior pituitary gland, unlike the posterior pitu-itary, is not derived from the brain and does not receivean axon tract from the hypothalamus. Nevertheless, thehypothalamus controls production and secretion of theanterior pituitary hormones. This control is exerted hor-monally rather than by means of nerve axons. Neurons inthe hypothalamus secrete releasing hormones and inhibit-ing hormones into blood capillaries at the base of the hy-pothalamus (figure 56.13). These capillaries drain intosmall veins that run within the stalk of the pituitary to asecond bed of capillaries in the anterior pituitary. Thisunusual system of vessels is known as the hypothalamohy-pophyseal portal system (another name for the pituitary isthe hypophysis). It is called a portal system because it hasa second capillary bed downstream from the first; the onlyother body location with a similar system is the liver,where capillaries receive blood drained from the gastroin-testinal tract (via the hepatic portal vein—see chapter 52).Because the second bed of capillaries receives little oxygenfrom such vessels, the vessels must be delivering some-thing else of importance.

Each releasing hormone delivered by the hypothalamo-hypophyseal system regulates the secretion of a specificanterior pituitary hormone. For example, thyrotropin-releasing hormone (TRH) stimulates the release of TSH,corticotropin-releasing hormone (CRH) stimulates the releaseof ACTH, and gonadotropin-releasing hormone (GnRH)stimulates the release of FSH and LH. A releasing hor-mone for growth hormone, called growth hormone–releasinghormone (GHRH) has also been discovered, and a releasinghormone for prolactin has been postulated but has thus farnot been identified.

The hypothalamus also secretes hormones that inhibitthe release of certain anterior pituitary hormones. To date,three such hormones have been discovered: somatostatin in-hibits the secretion of GH; prolactin-inhibiting factor (PIF ),found to be the neurotransmitter dopamine, inhibits the se-cretion of prolactin; and melanotropin-inhibiting hormone(MIH) inhibits the secretion of MSH.

Negative Feedback Control of Anterior PituitaryGland Secretion

Because hypothalamic hormones control the secretions ofthe anterior pituitary gland, and the anterior pituitary hor-mones control the secretions of some other endocrineglands, it may seem that the hypothalamus is in charge ofhormonal secretion for the whole body. This idea is notvalid, however, for two reasons. First, a number of en-docrine organs, such as the adrenal medulla and the pan-creas, are not directly regulated by this control system. Sec-ond, the hypothalamus and the anterior pituitary gland arethemselves partially controlled by the very hormoneswhose secretion they stimulate! In most cases this is an in-

hibitory control, where the target gland hormones inhibitthe secretions of the hypothalamus and anterior pituitary(figure 56.14). This type of control system is called nega-tive feedback inhibition and acts to maintain relatively con-stant levels of the target cell hormone.

Let’s consider the hormonal control of the thyroidgland. The hypothalamus secretes TRH into the hypothal-amohypophyseal portal system, which stimulates the ante-rior pituitary gland to secrete TSH, which in turn stimu-lates the thyroid gland to release thyroxine. Amongthyroxine’s many target organs are the hypothalamus andthe anterior pituitary gland themselves. Thyroxine actsupon these organs to inhibit their secretion of TRH andTSH, respectively (figure 56.15). This negative feedbackinhibition is essential for homeostasis because it keeps thethyroxine levels fairly constant.

To illustrate the importance of negative feedback in-hibition, we will examine a person who lacks sufficientiodine in the diet. Without iodine, the thyroid glandcannot produce thyroxine (which contains four iodinesper molecule). As a result, thyroxine levels in the bloodfall drastically, and the hypothalamus and anterior pitu-itary receive far less negative feedback inhibition than isnormal. This reduced inhibition causes an elevated se-cretion of TRH and TSH. The high levels of TSH stim-


Cell body

Axons toprimarycapillaries

Primarycapillaries

Pituitary stalk

Posterior pituitary

Anterior pituitaryHypophysealportal system

Portalvenules

FIGURE 56.13Hormonal control of the anterior pituitary gland by thehypothalamus. Neurons in the hypothalamus secrete hormonesthat are carried by short blood vessels directly to the anteriorpituitary gland, where they either stimulate or inhibit thesecretion of anterior pituitary hormones.

ulate the thyroid gland to grow, but it still cannot pro-duce thyroxine without iodine. The consequence of thisinterruption of the normal inhibition by thyroxine is anenlarged thyroid gland, a condition known as a goiter(figure 56.16).

Positive feedback in the control of the hypothalamusand anterior pituitary by the target glands is not commonbecause positive feedback cannot maintain constancy of theinternal environment (homeostasis). Positive feedback ac-centuates change, driving the change in the same direction.One example of positive control involves the control ofovulation, an explosive event that culminates in the expul-sion of the egg cell from the ovary. In that case, an ovarianhormone, estradiol, actually stimulates the secretion of ananterior pituitary hormone, LH. This will be discussed indetail in chapter 59.

The hypothalamus controls the anterior pituitary glandby means of hormones, and the anterior pituitary glandcontrols some other glands through the hormones itsecretes. However, both the hypothalamus and theanterior pituitary gland are controlled by other glandsthrough negative feedback inhibition.


Anterior pituitary

Hormones

Inhibition –

Inhibition –

Target glands

(Thyroid, adrenal cortex, gonads)

Hypothalamus

Releasing hormones(TRH, CRH, GnRH)

Tropic hormones(TSH, ACTH, FSH, LH)

Anterior pituitary

Negativefeedbackinhibition

Negativefeedbackinhibition

–

–

Thyroid gland

Thyroxine

Hypothalamus

TRH(Thyrotropin-releasing hormone)

TSH(Thyroid-stimulating hormone)

FIGURE 56.14Negative feedback inhibition. The hormones secreted by someendocrine glands feed back to inhibit the secretion ofhypothalamic releasing hormones and anterior pituitary tropichormones.

FIGURE 56.15Regulation of thyroxine secretion. The hypothalamus secretesTRH, which stimulates the anterior pituitary to secrete TSH.The TSH then stimulates the thyroid to secrete thyroxine, whichexerts negative feedback control of the hypothalamus and anteriorpituitary.

FIGURE 56.16A person with a goiter. This condition is caused by a lack ofiodine in the diet. As a result, thyroxine secretion is low, so thereis less negative feedback inhibition of TSH. The elevated TSHsecretion, in turn, stimulates the thyroid to grow and produce thegoiter.

The Thyroid andParathyroid GlandsThe endocrine glands that are regu-lated by the anterior pituitary, andthose endocrine glands that are regu-lated by other means, help to controlmetabolism, electrolyte balance, andreproductive functions. Some of themajor endocrine glands will be con-sidered in this section.

The Thyroid Gland

The thyroid gland (Greek thyros,“shield”) is shaped like a shield andlies just below the Adam’s apple in thefront of the neck. We have alreadymentioned that the thyroid gland se-cretes thyroxine and smaller amountsof triiodothyronine (T3), which stimu-late oxidative respiration in most cellsin the body and, in so doing, help setthe body’s basal metabolic rate (seechapter 51). In children, these thyroidhormones also promote growth andstimulate maturation of the centralnervous system. Children with under-active thyroid glands are thereforestunted in their growth and suffer se-vere mental retardation, a conditioncalled cretinism. This differs from pi-tuitary dwarfism, which results from inadequate GH and isnot associated with abnormal intellectual development.

People who are hypothyroid (whose secretion of thyrox-ine is too low) can take thyroxine orally, as pills. Only thy-roxine and the steroid hormones (as in contraceptive pills),can be taken orally because they are nonpolar and can passthrough the plasma membranes of intestinal epithelial cellswithout being digested.

There is an additional function of the thyroid gland thatis unique to amphibians—thyroid hormones are needed forthe metamorphosis of the larvae into adults (figure 56.17).If the thyroid gland is removed from a tadpole, it will notchange into a frog. Conversely, if an immature tadpole isfed pieces of a thyroid gland, it will undergo prematuremetamorphosis and become a miniature frog!

The thyroid gland also secretes calcitonin, a peptidehormone that plays a role in maintaining proper levels ofcalcium (Ca++) in the blood. When the blood Ca++ con-centration rises too high, calcitonin stimulates the uptakeof Ca++ into bones, thus lowering its level in the blood.Although calcitonin may be important in the physiologyof some vertebrates, its significance in normal human

physiology is controversial, and it appears less importantin the day-to-day regulation of Ca++ levels. A hormonethat plays a more important role in Ca++ homeostasis issecreted by the parathyroid glands, described in the nextsection.

The Parathyroid Glands and CalciumHomeostasis

The parathyroid glands are four small glands attached tothe thyroid. Because of their size, researchers ignored themuntil well into this century. The first suggestion that theseorgans have an endocrine function came from experimentson dogs: if their parathyroid glands were removed, the Ca++

concentration in the dogs’ blood plummeted to less thanhalf the normal value. The Ca++ concentration returned tonormal when an extract of parathyroid gland was adminis-tered. However, if too much of the extract was adminis-tered, the dogs’ Ca++ levels rose far above normal as thecalcium phosphate crystals in their bones was dissolved. Itwas clear that the parathyroid glands produce a hormonethat stimulates the release of Ca++ from bone.


56.4 Endocrine glands secrete hormones that regulate many body functions.

–35 –30 –25 –20 –15

Days from emergence of forelimb

–10 –5 0 +5 +10T

hyro

xine

sec

retio

n ra

te

TRH rises

Premetamorphosis

Rapid growthReduced growth,

rapid differentiationRapid differentiation

TRH TSH Thyroxine

Prometamorphosis Climax

FIGURE 56.17Thyroxine triggers metamorphosis in amphibians. In tadpoles at the premetamorphicstage, the hypothalamus releases TRH (thyrotropin-releasing hormone), which causes theanterior pituitary to secrete TSH (thyroid-stimulating hormone). TSH then acts on thethyroid gland, which secretes thyroxine. The hindlimbs then begin to form. Asmetamorphosis proceeds, thyroxine reaches its maximal level, after which the forelimbsbegin to form.

The hormone produced by the parathyroid glands is apeptide called parathyroid hormone (PTH). It is one ofonly two hormones in humans that are absolutely essentialfor survival (the other is aldosterone, which will be dis-cussed in the next section). PTH is synthesized and re-leased in response to falling levels of Ca++ in the blood.This cannot be allowed to continue uncorrected, because asignificant fall in the blood Ca++ level can cause severe mus-cle spasms. A normal blood Ca++ is important for the func-tioning of muscles, including the heart, and for properfunctioning of the nervous and endocrine systems.

PTH stimulates the osteoclasts (bone cells) in bone todissolve the calcium phosphate crystals of the bone matrixand release Ca++ into the blood (figure 56.18). PTH alsostimulates the kidneys to reabsorb Ca++ from the urine andleads to the activation of vitamin D, needed for the absorp-tion of Ca++ from food in the intestine.

Vitamin D is produced in the skin from a cholesterol de-rivative in response to ultraviolet light. It is called a vitamin

because a dietary source is needed to supplement theamount that the skin produces. Secreted into the bloodfrom the skin, vitamin D is actually an inactive form of ahormone. In order to become activated, the molecule mustgain two hydroxyl groups (—OH); one of these is added byan enzyme in the liver, the other by an enzyme in the kid-neys. The enzyme needed for this final step is stimulated byPTH, thereby producing the active form of vitamin Dknown as 1, 25-dihydroxyvitamin D. This hormone stimu-lates the intestinal absorption of Ca++ and thereby helps toraise blood Ca++ levels so that bone can become properlymineralized. A diet deficient in vitamin D thus leads topoor bone formation, a condition called rickets.

Thyroxine helps to set the basal metabolic rate bystimulating the rate of cell respiration throughout thebody; this hormone is also needed for amphibianmetamorphosis. Parathyroid hormone acts to raise theblood Ca++ levels, in part by stimulating osteoclasts todissolve bone.


Increased blood Ca++

Negativefeedback

Thyroid

Parathyroids

–

Low blood Ca++

Parathyroidhormone (PTH)

Increased absorptionof Ca++ from intestine(due to PTH activationof vitamin D)

Reabsorption of Ca++;excretion of PO3

4–

Osteoclasts dissolveCaPO4 crystals inbone, releasing Ca++

FIGURE 56.18Regulation of blood Ca++ levels by parathyroid hormone (PTH). When blood Ca++ levels are low, parathyroid hormone (PTH) isreleased by the parathyroid glands. PTH directly stimulates the dissolution of bone and the reabsorption of Ca++ by the kidneys. PTHindirectly promotes the intestinal absorption of Ca++ by stimulating the production of the active form of vitamin D.

The Adrenal GlandsThe adrenal glands are located just above each kidney (fig-ure 56.19). Each gland is composed of an inner portion, theadrenal medulla, and an outer layer, the adrenal cortex.

The Adrenal Medulla

The adrenal medulla receives neural input from axons ofthe sympathetic division of the autonomic nervous system,and it secretes epinephrine and norepinephrine in responseto stimulation by these axons. The actions of these hor-mones trigger “alarm” responses similar to those elicited bythe sympathetic division, helping to prepare the body for“fight or flight.” Among the effects of these hormones arean increased heart rate, increased blood pressure, dilationof the bronchioles, elevation in blood glucose, and reducedblood flow to the skin and digestive organs. The actions ofepinephrine released as a hormone supplement those ofnorepinephrine released as a sympathetic nerve neurotrans-mitter.

The Adrenal Cortex: Homeostasis of Glucose and Na+

The hormones from the adrenal cortex are all steroids andare referred to collectively as corticosteroids. Cortisol (alsocalled hydrocortisone) and related steroids secreted by theadrenal cortex act on various cells in the body to maintainglucose homeostasis. In mammals, these hormones are re-ferred to as glucocorticoids. The glucocorticoids stimulatethe breakdown of muscle protein into amino acids, whichare carried by the blood to the liver. They also stimulatethe liver to produce the enzymes needed for gluconeogene-sis, the conversion of amino acids into glucose. This cre-ation of glucose from protein is particularly important dur-ing very long periods of fasting or exercise, when bloodglucose levels might otherwise become dangerously low.

In addition to regulating glucose metabolism, the gluco-corticoids modulate some aspects of the immune response.Glucocorticoids are given medically to suppress the im-mune system in persons with immune disorders, such asrheumatoid arthritis. Derivatives of cortisol, such as pred-nisone, have widespread medical use as antiinflammatoryagents.

Aldosterone, the other major corticosteroid, is classi-fied as a mineralocorticoid because it helps regulate min-eral balance through two functions. One of the functionsof aldosterone is to stimulate the kidneys to reabsorb Na+

from the urine. (Urine is formed by filtration of bloodplasma, so the blood levels of Na+ will decrease if Na+ isnot reabsorbed from the urine; see chapter 58.) Sodium isthe major extracellular solute and is needed for the main-tenance of normal blood volume and pressure. Withoutaldosterone, the kidneys would lose excessive amounts ofblood Na+ in the urine, followed by Cl– and water; thiswould cause the blood volume and pressure to fall. Bystimulating the kidneys to reabsorb salt and water, aldo-sterone thus maintains the normal blood volume andpressure essential to life.

The other function of aldosterone is to stimulate thekidneys to secrete K+ into the urine. Thus, when aldos-terone levels are too low, the concentration of K+ in theblood may rise to dangerous levels. Because of these essen-tial functions performed by aldosterone, removal of theadrenal glands, or diseases that prevent aldosterone secre-tion, are invariably fatal without hormone therapy.

The adrenal medulla is stimulated by sympatheticneurons to secrete epinephrine and norepinephrineduring the fight-or-flight reaction. The adrenal cortexis stimulated to secrete its steroid hormones by ACTHfrom the anterior pituitary. Cortisol helps to regulateblood glucose and aldosterone acts to regulate bloodNa+ and K+ levels.


Cortex

Medulla

Ureter

Aorta

Left adrenalglandRight adrenal

gland

Rightkidney

Leftkidney

Vena cava

FIGURE 56.19The adrenal glands. The innerportion of the gland, the adrenalmedulla, produces epinephrine andnorepinephrine, which initiate aresponse to stress. The outerportion of the gland, the adrenalcortex, produces steroid hormonesthat influence blood glucose levels.

The PancreasThe pancreas is located adjacentto the stomach and is connectedto the duodenum of the small in-testine by the pancreatic duct. Itsecretes bicarbonate ions and a va-riety of digestive enzymes into thesmall intestine through this duct(see chapter 51), and for a longtime the pancreas was thought tobe solely an exocrine gland. In1869, however, a German medicalstudent named Paul Langerhansdescribed some unusual clusters ofcells scattered throughout thepancreas; these clusters came tobe called islets of Langerhans.Laboratory workers later ob-served that the surgical removal ofthe pancreas caused glucose to ap-pear in the urine, the hallmark ofthe disease diabetes mellitus. Thissuggested that the pancreas,specifically the islets of Langer-hans, might be producing a hor-mone that prevents this disease.

That hormone is insulin, se-creted by the beta (β) cells of theislets. Insulin was not isolateduntil 1922, when two young doc-tors working in a Toronto hospi-tal succeeded where many othershad not. On January 11, 1922,they injected an extract purifiedfrom beef pancreas into a 13-year-old diabetic boy, whoseweight had fallen to 65 pounds and who was not expectedto survive. With that single injection, the glucose level inthe boy’s blood fell 25%. A more potent extract soonbrought the level down to near normal. The doctors hadachieved the first instance of successful insulin therapy.

Two forms of diabetes mellitus are now recognized. Peo-ple with type I, or insulin-dependent diabetes mellitus, lackthe insulin-secreting β cells. Treatment for these patientstherefore consists of insulin injections. (Because insulin is apeptide hormone, it would be digested if taken orally andmust instead be injected into the blood.) In the past, onlyinsulin extracted from the pancreas of pigs or cattle wasavailable, but today people with insulin-dependent diabetescan inject themselves with human insulin produced by ge-netically engineered bacteria. Active research on the pos-sibility of transplanting islets of Langerhans holds muchpromise of a lasting treatment for these patients. Most di-abetic patients, however, have type II, or non-insulin-dependent diabetes mellitus. They generally have normalor even above-normal levels of insulin in their blood, buttheir cells have a reduced sensitivity to insulin. These

people do not require insulin injections and can usuallycontrol their diabetes through diet and exercise.

The islets of Langerhans produce another hormone; thealpha (α) cells of the islets secrete glucagon, which acts an-tagonistically to insulin (figure 56.20). When a person eatscarbohydrates, the blood glucose concentration rises. Thisstimulates the secretion of insulin by β cells and inhibits thesecretion of glucagon by the α cells. Insulin promotes thecellular uptake of glucose into liver and muscle cells, whereit is stored as glycogen, and into adipose cells, where it isstored as fat. Between meals, when the concentration ofblood glucose falls, insulin secretion decreases andglucagon secretion increases. Glucagon promotes the hy-drolysis of stored glycogen in the liver and fat in adiposetissue. As a result, glucose and fatty acids are released intothe blood and can be taken up by cells and used for energy.

The β cells of the islets of Langerhans secrete insulin,and the α cells secrete glucagon. These two hormoneshave antagonistic actions on the blood glucoseconcentration; insulin lowers and glucagon raises bloodglucose.


Blood glucosedecreased

Blood glucoseincreased

Glucose moves fromblood into cells

Insulin secretion increasedGlucagon secretion decreased

Insulin secretion decreasedGlucagon secretion increased

Negativefeedback

Negativefeedback

Glycogen hydrolyzedto glucose, thensecreted into blood

Islets of Langerhans

– –

Between mealsAfter a meal

Liver

FIGURE 56.20The antagonistic actions of insulin and glucagon on blood glucose. Insulin stimulates thecellular uptake of blood glucose into skeletal muscles and the liver after a meal. Glucagon stimulatesthe hydrolysis of liver glycogen between meals, so that the liver can secrete glucose into the blood.These antagonistic effects help to maintain homeostasis of the blood glucose concentration.

Other Endocrine GlandsSexual Development, Biological Clocks, andImmune Regulation in Vertebrates

The ovaries and testes are important endocrine glands,


Chapter 56 Summary Questions Media Resources

56.1 Regulation is often accomplished by chemical messengers.

• Endocrine glands secrete hormones into the blood,which are then transported to target cells.

• Hormones may be lipophilic, such as the steroidhormones and thyroxine, or polar, such as amine,polypeptide, and glycoprotein hormones.

• Prostaglandins and other paracrine regulatorymolecules are produced by one cell type and regulatedifferent cells within the same organ.

1. What is the definition of ahormone? How do hormonesreach their target cells? Why areonly certain cells capable ofbeing target cells for a particularhormone?2. How do hormones andparacrine regulators differ fromone another?

• Lipid-soluble hormones enter their target cells, bindto intracellular receptor proteins, and the complexthen binds to hormone response elements on theDNA, activating specific genes.

• Polar hormones do not enter their target cells, butinstead bind to receptor proteins on the cellmembrane and activate second-messenger systems orcontrol ion channels.

3. How does epinephrine resultin the production of cAMP in itstarget cells? How does cAMPbring about specific changesinside target cells?

56.2 Lipophilic and polar hormones regulate their target cells by different means.

• Axons from neurons in the hypothalamus enter theposterior pituitary, carrying ADH and oxytocin; theposterior pituitary stores these hormones and secretesthem in response to neural activity.

• The anterior pituitary produces and secretes a varietyof hormones, many of which control other endocrineglands; the anterior pituitary, however, is itselfcontrolled by the hypothalamus via releasing andinhibiting hormones secreted by the hypothalamus.

4. Where are hormones secretedby the posterior pituitary glandactually produced?5. Why are the hormones of theanterior pituitary gland calledtropic hormones? 6. How does the hypothalamusregulate the secretion of theanterior pituitary?

56.3 The hypothalamus controls the secretions of the pituitary gland.

• The thyroid secretes thyroxine and triiodothyronine,which set the basal metabolic rate by stimulating therate of cell respiration in most cells of the body.

• The adrenal cortex secretes cortisol, which regulatesglucose balance, and aldosterone, which regulatesNa+ and K+ balance.

• The β cells of the islets of Langerhans in the pancreassecrete insulin, which lowers the blood glucose;glucagon, secreted by the α cells, raises the bloodglucose level.

7. What hormones are producedby the adrenal cortex? Whatfunctions do these hormonesserve? What stimulates thesecretion of these hormones?8. What pancreatic hormone isproduced when the body’s bloodglucose level becomes elevated?

56.4 Endocrine glands secrete hormones that regulate many body functions.

BIOLOGY

RAVEN

JOHNSON

S I X T H

E D I T I O N

www.mhhe.com/raven6ch/resource28.mhtml

• Art Activity: –Endocrine System

• Endocrine SystemRegulation

• Peptide HormoneAction

•Activity:–Peptide Hormones–Steroid Hormones

• Types of Hormones

• Portal System

• Hypothalamus• Pituitary Gland

• Parathyroid Hormone• Glucose Regulation

• Thyroid Gland• Parathyroid Glands• Adrenal Glands• Pancreas

Documents

56 - Welcome to MHHE