BARBARA R. LANDAU '
`
`‘R...
`
`A
`"
`I
`T
`I SECON5 EDITION
`ESSENTIAL HUMAN ANATOMY
`ANIL PHYSIOLOGY
`
`
`
`GENENTECH 2009
`GENZYME V. GENENTECH .
`IPR2016-00383’
`‘V\,
`
`.
`
`.
`
`GENENTECH 2009
`GENZYME V. GENENTECH
`IPR2016-00383
`
`

`
`Barbara R. Landau
`
`University of Washington
`
`Essential Human Anatomy
`and Physiology
`
`Second Edition
`
`Scott, Foresman and Company
`
`Glenview, iilinois
`' Dallas, Tex.
`Oakland, N..J.
`Palo Alto, Cal.
`Tucker, Ga.
`
`London, England
`
`

`
`13
`
`Nature of Hormones and Hormone Action
`
`The Pituitary Gland and Hormone Control
`
`Endocrine Glands and Their Secretions
`
`The Endocrine Glands as a
`Control System
`
`Preceding chapters have been devoted to the role of
`the nervous system in the control of body functions.
`As important as it is, and as widespread as its
`actions are, the nervous system does not, however,
`control everything. There is another control system,
`the endocrine system, whose actions are also vital to
`our well—being and, indeed, to our very existence.
`Most of the body’s systems consist of several
`anatomically connected organs and structures
`organized to perform important and specific
`functions for the entire body. The organs of the
`endocrine system seem to be relatively independent
`of one another, anatomically and functionally.
`Though they are n.ot an organ system in the usual
`sense, the endocrine glands do share a common
`mode of action: instead of conducting impulses, they
`secrete hormones which affect many cell functions
`that are not under neural control. Together the
`endocrine glands constitute a control system that
`parallels, but does not duplicate, the nervous system.
`In this chapter we discuss how hormones act and
`examine the characteristics common to all endocrine
`controls. The individual glands and their hormones
`are discussed in a rather general way, with the
`specific details added later in the sections covering
`the processes that each hormone helps to regulate.
`
`352
`
`
`
`

`
`Nature of Hormones and Hormone Action 353
`
`
`TABLE 13-1
`
`THE ENDOCRINE GLANDS
`
`Pituitary gland (hypophysis)
`anterior lobe (adenohypophysis)
`posterior lobe (neurohypophysis)
`intermediate lobe
`
`Adrenal glands
`adrenal medulla
`adrenal cortex
`
`Thyroid gland
`
`Parathyroid gland
`
`Pancreatic islands (islets of Langerhans)
`Gonads
`testis
`ovary
`Placenta
`
`Digestive tract (stomach, small intestine)
`Kidney
`
`Pineal gland (?)
`
`The endocrine system includes the
`glands listed in Table 13-1. All endo-
`crine glands act by secreting their hor-
`mones into the bloodstream for distri-
`
`bution throughout the entire body. In
`contrast, exocrine glands such as the
`salivary glands or sweat glands release
`their secretions directly (or via a duct)
`onto the surface of the body (or one of
`its inward extensions). An endocrine
`gland is therefore considered to be a
`specific organ whose bloodborne secre-
`tion produces a specific action on an
`organ (the target organ) at some dis-
`tance from the gland itself.‘
`
`NATURE OF HORMONES
`AND HORMONE ACTION
`
`Hormones affect all types of cells,
`not just the usual effectors. They do so
`chiefly by altering a basic cell activity in
`some way, and this affects the rate of a
`particular process that may be an essen-
`tial part of the body economy. The re-
`sults from hormonal actions are many
`
`‘By this definition, such important chemical regu-
`lators as acetylcholine or carbon dioxide are excluded,
`since acetylcholine is not carried in the blood to a distant
`site and carbon dioxide is not secreted by a specific or-
`gan. They remain chemical regulators, but they are not
`hormones.
`
`and varied, but they can be fitted into
`four broad categories:
`the
`1. Hormones help regulate
`energy supply, including processes by
`which the energy is obtained from
`foodstuffs (or stored reserves). Thus
`they help control the digestive system,
`and they are of major importance in
`regulating metabolism and energy re-
`lease from foodstuffs after they have
`been digested and have entered the
`bloodstream.
`
`2. Hormones help control certain
`properties of the extracellular fluid (the
`internal
`environment).
`Specifically,
`they help control
`the metabolism of
`water and electrolytes; that is, they de-
`termine the fate of much of the sodium,
`
`potassium, calcium, phosphorus, and
`water in the body.
`3. Hormones help us cope with
`adverse conditions or stresses, includ-
`ing such adversities as cold, heat, de-
`hydration,
`trauma, blood loss, and
`emotional stress,
`in terms of with-
`standing the stress,
`fighting it, or
`escaping from it.
`4. Hormones help regulate such
`basic aspects of life as growth, develop-
`ment, and reproduction.
`
`Formation and Transport
`of Hormones
`
`The chemical nature of many hor-
`mones is known, including their mo-
`lecular structure. Many of those identi-
`fied are protein derivatives, either
`amines, peptides, or polypeptides. Amines
`are
`small molecules, essentially an
`amino acid with the carboxyl
`(acid)
`group removed and perhaps a small
`side chain added. Peptides consist of a
`few amino acids, and polypeptides are
`longer chains of amino acids. They have
`many of the properties of proteins, in
`terms of the kinds of reactions they can
`enter into, but, of course, they are much
`smaller molecules.
`
`Protein—related hormones are pro-
`duced in the manner described in
`
`Chapter 2 for general protein synthesis.
`The short amino acid chains are assem-
`
`bled on ribosomes of rough endoplas-
`mic reticulum and are transported in
`the ER to the Golgi apparatus where
`they are packaged into secretion gran-
`
`

`
`354 The Endocrine Glands as a Control System
`
`
`ules to be held until the proper stimu-
`lus causes their release from the cell.
`
`The other major group of hor-
`mones are steroids. These hormones
`
`contain the basic steroid nucleus (a
`specific molecular configuration),
`so
`they are all quite similar, but they differ
`in slight but important specific groups
`attached at certain sites (see Figure
`13-7). One important property of ste-
`roids is that they are lipid derivatives so
`they are fat soluble and thus can diffuse
`through cell membranes. Steroid hor-
`mones are synthesized from cholesterol
`(a widely distributed steroid) partly in
`mitochondria and partly in smooth ER.
`Important steroid hormones are those
`of the adrenal cortex, ovary, testis, and
`some of those produced by the pla-
`centa.
`Since hormones reach their desti-
`
`nation by traveling in the bloodstream,
`much attention has been given to the
`concentration of hormones
`in the
`
`blood. Many of the advances in endo-
`crinology have come on the heels of
`better ways to measure the hormone
`levels in the blood. This is often a diffi-
`
`cult problem for, although hormones
`are potent substances, they are present
`in very small amounts?
`Even knowing the exact concentra-
`tion of a hormone in the blood does not
`
`tell us very much, because hormones do
`not exert their action in the blood; the
`blood is merely a transport system for
`most of them. Hormones in the blood
`
`are on their way either to some place or
`from some place. The amount of hor-
`mone in the blood at any given time
`depends upon the rate at which it is
`entering the blood (rate of secretion)
`
`’Some, such as amines (epinephrine), can be
`measured directly by chemical analysis. Some are detect-
`ed by bioassay, a method used to measure a hormone
`when its chemical nature is not known. A bioassay con-
`sists of comparing a biological effect (such as the increase
`in the weight of an organ) of a sample containing an
`unknown amount of a hormone sample with the effect of
`a known amount of that hormone. A newer, extremely
`sensitive method is the radiaimmunoassay, which makes
`use of the fact that proteins are bound firmly by specific
`antibodies. A sample containing an unknown amount of
`a hormone would interfere with the binding of a known
`amount of a pure sample. By determining the extent of
`the interference, the amount of hormone in the unknown
`sample can be determined. To do so, the pure sample
`carries a radioactive label, which can be measured very
`accurately. This method is applicable to protein and to
`peptide hormones.
`
`and the rate at which it is leaving the
`blood, either by excretion or inactiva-
`tion. Many hormones are inactivated in
`the liver or elsewhere, and many are
`excreted rather rapidly in the urine. In
`fact, the half-life (the length of time for
`one half of a given dose to disappear
`from the blood) varies from a few min-
`utes to a few hours, and averages only
`10— 30 minutes.
`The fact
`that hormones are re-
`
`moved so rapidly suggests that in order
`to maintain a blood level, production
`must be continual. This is the case, for
`they are produced continually, but not
`necessarily at a constant rate. Stimula-
`tion of an endocrine gland increases the
`ongoing rate of production, and inhibi-
`tion reduces it. The need for continual
`
`production is all the more important
`when one realizes that, with one or two
`exceptions, we do not store hormones
`to any great extent. Except for the thy-
`roid hormones, only a one- or two—day
`supply is on hand.
`Most hormones are bound to pro-
`teins as they are transported in the
`blood. It is a reversible condition, and
`
`an equilibrium is maintained between
`the free hormone and the bound hor-
`mone:
`
`Free hormone + plasma protein
`/
`(2 Protein-bound hormone
`Action
`
`Some hormones are nearly 95 percent
`bound while others are more nearly
`half and half. Only the free portion can
`act, or be acted upon. When some of the
`free hormone is inactivated or leaves
`the bloodstream, more is released from
`the protein and the free/ bound equilib-
`rium is maintained. Such binding
`serves a purpose, for bound hormones
`are not available to diffuse out of the
`blood vessel or to be excreted in the
`urine.
`
`Mechanisms of
`Hormone Action
`
`Depending upon how one chooses
`to classify or count, there may be 40 to
`50 different hormones with many dif-
`ferent actions, but
`surprisingly, of
`those whose mechanism of action is
`
`known, all seem to involve only two or
`three different mechanisms.
`
`

`
`Nature of Hormones and Hormone Action 355
`
`
`As far as is known at present, all
`hormone actions begin with the com-
`bining or binding of the hormone with
`a specific receptor site of the target cell,
`in a manner somewhat similar to the
`
`transmitter substances at
`binding of
`neuromuscular junctions and synapses.
`Therefore, a hormone can only act on a
`cell that has receptor sites specifically
`for that hormone. This is the way in
`which the hormone ”recognizes” its
`target cell (or vice versa), and it is the
`mechanism that limits the action of a
`
`hormone to certain target cells. The re-
`ceptors have been described as either
`fixed receptors or mobile receptors.
`
`Fixed Receptors For hormones
`that bind to fixed receptors,
`the re-
`ceptors are on the outer surface of
`the cell membrane. The hormone binds
`there and never enters the cell. The
`
`hormone—receptor combination serves
`to activate an enzyme that is also in the
`cell membrane, but presumably on its
`inner surface (Figure 13—1A). This en-
`zyme, adenyl cyclase, acts upon adeno-
`sine triphosphate (ATP) in the cell cyto-
`plasm, converting it to a cyclic form,
`cyclic AMP (CAMP):
`
`cAMP—«CycIic Adenosine 3'5’ Monophosphate
`
`NH2
`
`N
`
`N/
`
`I
`
`\
`N
`.
`adenine
`
`\
`
`O
`OH OH
`H
`I
`I
`I
`N—-(ll-(I3-C-—-C-C
`I
`I
`H
`H
`H H\OO
`ribose
`
`O:-P phosphate
`IOH
`
`Cyclic AMP is inactivated rather quicl<~
`ly, but before that happens, CAMP
`causes an action which, in most if not
`all cases, is the activation of a protein
`kinase. Protein kinase describes a class
`
`of enzymes that activates another en-
`zyme by transfering phosphate (from
`ATP) to it. The action that occurs when
`a protein kinase is activated depends
`upon the action of the enzyme it acti-
`vates. Therefore,
`the effect of a hor-
`mone (which is specific) depends upon
`the action of a particular protein kinase
`(which is also specific). The link be-
`tween them is the adenyl cyclase and
`cyclic AMP, and they are the same in
`many hormone actions.
`Because cAMP is inactivated rather
`
`quickly, more hormone is needed and
`
`Mechanisms of hormone action. A. Fixed receptor model. B. Mobile
`
`FIGURE 13-1
`receptor model.
`
`Hormone
`
`RBCGDIOV SW0
`
`.
`Cell membrane
`
`.
`
`/—\denyl cyclase
`
`Inactive
`protein Kinase
`
`Hormone
`
`C
`
`Cell membrane
`*4‘
`
`-il-
`
`Synthesis ol
`protein ierizyrne)
`
`3% Large receptor protein
`G?
`Specific
`IRNA
`small protein
`
` Cell nu(:Ietis
`
`
`
`
`
`i
`
`orrn
`
`l
`I J
`
`,
`I‘lWaC'.IV€
`
`F
`
`II
`
`L
`
`Active
`QVOIGITW KIHEISG
`
`Specific action
`
`

`
`356 The Endocrine Glands as a Control System
`
`more CAMP must be produced to con-
`tinue the action (in much the same way
`that additional packets of acetylcholine
`must be continually released if a muscle
`contraction is to be maintained). Epi-
`nephrine is one of about a dozen hor-
`mones known to act by way of CAMP.
`In fact, studies on how epinephrine
`causes glucose to be released from the
`liver led to the discovery of the role of
`adenyl cyclase and CAMP in the first
`place. Cyclic AMP is sometimes called
`the ”second messenger,” the hormone
`being the ”first messenger.”
`
`Mobile Receptors Mobile recep-
`tors are involved in the action of steroid
`hormones. Recall
`that as lipid sub-
`stances, steroids can pass through the
`cell membrane. The receptor site for
`steroid hormones is in the cytoplasm of
`the cell, and they diffuse into the cell
`and bind to the site (Figure 13- 1B). The
`hormone—receptor combination then
`moves into the nucleus of the cell where
`it combines with a smaller protein
`which enables it to have an action on
`the DNA of the nucleus. The DNA of a
`particular gene unwinds leading to the
`synthesis of mRNA that carries the
`code for
`a particular‘ protein. The
`mRNA moves to the cytoplasm, and
`that protein is synthesized at the ribo-
`somes. The new protein is generally an
`enzyme to catalyze a particular reac-
`tion.
`
`In either case, the varied effects of a
`hormone, whether brought about by
`fixed or mobile receptors, result in the
`presence of more active enzymes, thus
`accelerating (or blocking) a particular
`cellular reaction, which we describe as
`the action of that hormone.
`
`Other Possible Mechanisms of
`Action A third mode of action in-
`volves an alteration in the properties of
`the cell membrane, so as to increase the
`permeability of the membrane to a spe-
`cific substance. One of the best—known
`examples
`is
`the hormone
`insulin,
`which increases the rate of entry of glu-
`cose into the cells. Some hormones that
`act in this way do so by way of CAMP,
`but others do not and their mechanism
`of action is not understood.
`
`A final possible mechanism of ac-
`tion has been postulated. It is not un—
`derstood yet, but it could explain the
`fact that some hormones alter the effec-
`tiveness of another hormone. It is sug-
`gested that the action may come about
`by an effect on the receptor sites.
`If
`hormone A "destroys receptors for hor-
`mone B, or occupies them leaving no
`place for hormone B to bind, the effec-
`tiveness of hormone B will be greatly
`reduced. Some hormones have what is
`called a permissive action. They do not
`bring about a particular effect by them-
`selves, but their presence is necessary
`for another hormone to be fully effec-
`tive. One possible explanation (there
`are others) might be that the permissive
`action of hormone A could have a favor-
`able effect on the binding sites for hor-
`mone B.
`
`Prostaglandins and Hormone Ac-
`tions Prostaglandins are among the
`most confusing substances we will en-
`counter in the body! The confusion
`begins with their name. Prostaglandins
`were first discovered in semen, the se-
`cretion of the male reproductive tract,
`and were presumably produced by the
`prostate gland, hence the name.
`It
`turned out
`that
`the seminal vesicles
`are the chief source of prostaglandins in
`semen, but the name has stuck. Prosta-
`glandins are not hormones, but they are
`often considered with them (partly for
`lack of a better category), and their ac-
`tions are related to hormone action in
`several ways.
`Prostaglandins are synthesized by
`most, if not all, cells of the body. There
`are more than a dozen different pros-
`taglandins, differing only slightly in
`their molecular configuration (and in
`some actions). They are all derivatives
`of a 20-carbon fatty acid and are there-
`fore lipid—soluble and able to diffuse
`through cell membranes. Prostaglan-
`dins are extremely potent substances,
`but are present in very small amounts,
`more so in some tissues or at certain
`times. They are present in the blood,
`probably entering by diffusion rather
`than actually being secreted into it, but
`they are rapidly inactivated, especially
`in the lungs, liver, and kidney.
`Prostaglandins
`are
`almost
`
`as
`
`

`
`Nature of Hormones and Hormone Action
`
`
`357
`
`FlGURE 13—2
`Negatve feedback
`contro of hormone
`secretion. A. Direct
`action. as in control of
`insulir secretion by the
`blood glucose level.
`B. Indirect action, as in
`contro of thyroid
`hormone secretion by
`its effect upon
`secreton of thyroid
`stimulating hormone
`(TSH) by the anterior
`pituita y.
`
`widely distributed as ATP, but their
`actions are so varied that it is almost
`
`impossible to find a common thread
`among them. Since they are produced
`by virtually all cells, and since their ac-
`tions seem to be local (that is, within
`”diffusing distance" rather than requir-
`ing a transport medium), it is assumed
`that they exert their effects locally» in
`the cell or its immediate vicinity. They
`have actions on some part of nearly
`every organ system, but their actions
`on the reproductive, cardiovascular,
`and digestive systems seem to have
`received the most attention. One of
`
`their actions, for example, is to inhibit
`smooth muscle in blood vessels, which
`dilates the vessels and reduces the
`
`blood pressure. But they also cause con-
`traction of other smooth muscle, such
`as in the digestive tract and uterus.
`These and other actions have prompted
`investigations into their possible value
`for a number of applications ranging
`from treatment of high blood pressure
`to inducing labor.
`When all the effects of the prosta-
`glandins are tabulated, it is noted that
`most
`if not all actions are those in
`
`which CAMP is involved. Prostaglan—
`dins increase the content of CAMP in
`most cases, but there are a few tissues
`in which they decrease the amount of
`CAMP. By altering the formation of
`CAMP in cells the prostaglandins can
`affect the response of those cells to a
`hormone whose action involves CAMP.
`
`Prostaglandins may turn out to be local
`modulators
`of CAMP-induced reac-
`tions. It remains to be seen what con-
`
`trols the production of the prostaglar1—
`dins.
`
`Control of Hormone Secretion
`
`The rate of secretion of an endo-
`
`regulated by neural
`crine gland is
`and/or chemical means. A number of
`
`endocrine glands are innervated by
`autonomic fibers, chiefly parasympa-
`thetic, but for the most part these nerves
`exert only secondary control. Cutting
`the nerve does not have much effect on
`
`the secretion of the gland, and stimula-
`tion may only raise the level of secre-
`tion slightly.
`One endocrine gland, however,
`
`Panr:ieas
`
`
`
`
`Blccd glticcsr:
`level
`
`
`
`iyrc=o
`
`and
`
`T».y.O,d
`hormone
`
`+
`
`O7 COl7SUl““L>‘. on by ood, cells
`
`B
`
`receives an important nerve supply.
`That is the adrenal medulla, which re-
`ceives sympathetic innervation by a
`preganglionic neuron, and secretion by
`the adrenal medulla is part of the re-
`sponse of the sympathetic nervous sys-
`tem. (Recall that epinephrine, the hor-
`mone produced by the adrenal medulla,
`resembles norepinephrine, the sympa-
`thetic postganglionic transmitter, both
`chemically and in the action produced.)
`In addition,
`the release of hormones
`
`from the posterior lobe of the pituitary
`gland is directly controlled by neurons
`from the brain in a unique manner, to
`be discussed below.
`
`The major control of endocrine
`glands is chemical in nature. It is exert-
`ed by what
`is known as a negative
`feedback mechanism. The
`simplest
`form is a direct feedback such as in the
`control of the secretion of insulin. The
`overall effect of insulin is to lower the
`
`blood glucose level. Elevation of the
`blood glucose concentration causes in-
`creased production of
`insulin, which
`causes glucose to leave the blood and
`enter cells. As the level of glucose in the
`blood falls, there is less stimulation of
`the pancreas, insulin secretion declines,
`and the blood glucose level begins to
`rise once more (Figure 13—2A). When
`
`
`
`

`
`358 The Endocrine Glands as a Control System
`
`O
`
`«
`
`' 0‘
`
`i
`
`/f~
`‘ ‘\ pmCmasm
`
`O
`
`-
`
`Supraoptic nucleus
`
`Anterior hypomaiamus
`
`Anterior lobe
`(adenonypopnysis)
`
`/
`
`$/
`
`.
`
`iT
`
`I
`
`.
`
`Mamiilarybody
`
`Paraventricuiar nucleus
`Pituitary stalk
`(|FilU“dibUlU‘m)
`
`Posterior lobe
`(neuronypopnysis)
`
`Intermediate lobe
`
`FIGURE 13-3
`
`The pituitary gland and its innervation.
`
`blood glucose is made to fluctuate by
`other factors (such as eating or exer-
`cise),
`the secretion of
`insulin is ad-
`justed to reduce the magnitude of the
`fluctuations of glucose concentration.
`Negative feedback mechanisms
`are
`designed to maintain the status quo, to
`prevent change or, if change occurs, to
`bring things back to ”normal.” Thus,
`negative feedback is
`a homeostatic
`mechanism.
`
`Several endocrine glands are con-
`trolled by a more indirect version of the
`same mechanism, as illustrated by the
`thyroid gland (Figure 13—2B). Thyroid
`secretion is stimulated by a hormone
`from the anterior pituitary known ap--
`propriately as the thyroid-stimulating
`hormone (TSH). A high level of thyroid
`hormone in the blood inhibits the pi-
`tuitary secretion of TSH, which results
`in less stimulus for secretion of the thy-
`roid hormone. Soon there is less of the
`
`latter to inhibit the production of TSH,
`and as TSH rises, the thyroid gland se-
`cretes more of its hormone.
`
`the pituitary
`The implication of
`gland in the control of endocrine secre-
`
`tion is a rather complex subject that
`requires further consideration for two
`reasons. First,
`the anterior pituitary
`gland produces hormones that stimu-
`late
`secretion
`by other
`endocrine
`glands, and it is regulated by the secre-
`tions of
`those glands
`(by negative
`feedback). Second,
`the pituitary is an
`important
`link between the nervous
`system and the endocrine system.
`
`THE PITUITARY GLAND
`AND HORMONE CONTROL
`
`a
`The pituitary gland occupies
`unique
`position
`among
`endocrine
`glands because of its role in the control
`of secretion by other endocrine glands.
`It also has a unique association with the
`nervous system—part of it (the neuro-
`hypophysis) is actually part of the dien—
`cephalon. The anterior portion (adeno-
`hypophysis) also has close ties with the
`brain. These connections regulate se-
`cretion by the pituitary, and therefore
`also the secretion by those glands con-
`trolled by the anterior pituitary. Be—
`cause the pituitary gland has a special
`role in the overall regulation of hor-
`mone secretion,
`it
`is considered in
`some detail at this time.
`
`Anatomy of the Pituitary
`Gland
`
`The pituitary gland (hypophysis),
`safely hidden in the sella turcica of the
`sphenoid bone (see Figure 10—3),
`is
`three essentially separate glands,
`the
`anterior, posterior, and intermediate
`lobes (Figure 13-3). The posterior lobe,
`or neurohypophysis, is an outgrowth of
`the brain. It is connected directly to the
`brain by the pituitary stalk (infumilibw
`lum), and a tiny extension of the third
`ventricle of
`the brain can often be
`traced into the stalk and into the neuro-
`
`hypophysis itself. The posterior lobe
`contains relatively few cells and does
`not
`look much like glandular tissue.
`The anterior lobe, or adenohypophysis,
`develops embryologically as an isolated
`outgrowth of
`the primitive gut and
`migrates toward the neurohypophysis;
`it has a glandular appearance, with
`cords of several
`types of cells inter-
`
` ——j
`
`

`
`
`
`The Pituitary Gland and Hormone Control 359
`
`\/
`
`Optic chiasm
`
`gSuperior
`hypopnyseal artery
`
`/
`//
`l
`‘
`
`
`
`Posterior
`
`hypopnyseai
`veins
`
`l
`
`T
`
`,
`
`‘
`
`t
`
`’
`
`~
`
`w__L___/,
`
`interior hi/pop yseal artery
`
`Anterior
`
`i
`i
`
`tiypophysegai
`vein
`
`Anterior hypophyseai veins
`
`FIGURE 13—4
`
`The blood supply of the pituitary.
`
`”master” gland. It is not, however, real-
`ly in decisive control of the ’’lesser’’
`glands; it relays messages, and it is it-
`self controlled by the hypothalamus,
`which secretes minute amounts of spe-
`cific substances called releasing hor-
`mones into the blood of the hypophy—
`seal portal system. Upon reaching the
`anterior pituitary, each releasing hor-
`mone causes secretion of one of the
`
`anterior lobe hormones (Figure 13 — 5).
`Releasing hormones
`that have
`been identified include a growth hor-
`mone-releasing hormone (GRH), a pro-
`lactin-releasing hormone (PRF), a thy-
`rotropin-releasing
`hormone
`(TRF),
`a
`eorticotropin-releasing hormone
`(CRF),
`a
`folh'cle—stz'mulating hormone-releasing
`hormone (FRH), and a luteinizing hor-
`mone—releasz'ng hormone (LRH), although
`there is some question as to whether
`FRH and LRH are actually two different
`substances. There is also a hormone
`
`inhibits the release of growth
`that
`hormone (GIH or somatostatin) and pro-
`lactin (PIH). There may also be a
`releasing hormone
`for melanocyte—
`stimulating hormone (MSH) produced
`
`spersed with networks of vascular sinu-
`soids. The intermediate lobe arises
`
`where the anterior and posterior por-
`tions of the developing pituitary come
`into contact with one another.
`
`The neurohypophysis receives a
`prominent nerve supply in the several
`short fiber tracts that enter it by way of
`the pituitary stalk. These bundles arise
`in specific nuclei of the hypothalamus
`where the neurons have their
`cell
`
`bodies, and end near capillaries in the
`posterior lobe. Despite many persistent
`attempts
`to
`demonstrate
`secretory
`nerves,
`the adenohypophysis has no
`known innervation other than a few au-
`
`tonomic fibers to the blood vessels.
`its
`The posterior
`lobe
`receives
`blood supply from tiny branches of the
`internal carotid artery (Figure l3—4).
`Arteries for the anterior lobe first form
`
`a network of capillary loops in the infe-
`rior portion of the hypothalamus. These
`capillaries then converge to form the
`several vessels of the hypophyseal por-
`tal system that descend along the stalk
`and drain into the sinusoidal capillaries
`in the adenohypophysis. Blood reach-
`ing the anterior lobe has therefore al-
`ready passed through one capillary bed
`in the nearby hypothalamus.
`The hormones secreted by the pi-
`tuitary gland and their main actions are
`shown in Table 13-2. Over the years,
`other ”factors” or ”principles” have
`been attributed to the anterior lobe, but
`these effects are now generally believed
`to belong to the known pituitary hor-
`mones. Of those produced by the ante-
`rior pituitary, only the growth hormone
`and prolactin (in humans) do not have
`another endocrine gland as their target
`organ. FSH and LH, the gonadotropins,
`affect the gonads (ovary and testis), but
`they do much more than stimulate
`hormone secretion by the gonads. Pro-
`lactin has sometimes been considered
`
`to be a gonadotropin because in female
`rodents (especially the much—studied
`laboratory rat) it affects the gonad (lu-
`teotropic action), but this action is lack-
`ing in humans.
`
`Control of Pituitary Secretion
`
`Because the adenohypophysis con-
`trols the activity of several other endo-
`crine glands, it has often been called the
`
`
`
`

`
`360 The Endocrine Glands as a Control System
`
`
`TABLE 13-2
`
`THE PITUITARY HORMONES AND THEIR ACTIONS
`
`Hormone
`
`Other Names
`
`Major Action
`
`Adenohypophysis
`Growth hormone
`
`Thyroid-stimulating
`hormone
`
`Adrenocorticotropic
`hormone
`
`Fo|lio|e—stimu|ating
`hormone
`
`Luteinlzing hormone
`
`Prolactin
`
`GH; somatotropin,
`somatotropic hormone
`
`TSH; thyrotropin
`
`stimulates growth of body
`
`stimulates thyroid growth and
`secretion
`
`ACTH; corticotropin
`
`stimulates growth and secretion by
`adrenal cortex
`
`FSH; gonadotropin
`
`LH; interstitial cell-
`stimulating hormone,
`ICSH; gonadotropin
`
`lactogenic hormone,
`luteotropic hormone,
`LTH
`
`stimulates growth of ovarian follicle
`in female and spermatogenesis in
`male
`
`stimulates ovulation, formation of
`corpus luteum, and hormone
`secretion in female; stimulates
`secretion by interstitial cells in male
`stimulates secretion of milk; maintains
`corpus luteum in female rodents
`
`Neurohypophysis
`Antidiuretic hormone
`
`ADH; vasopressin
`
`Oxytocin
`
`—
`
`promotes water reabsorption from
`collecting tubule of kidney
`stimulates milk ejection, and
`contraction of pregnant uterus
`
`Intermediate lobe
`Melanocyte—stimulating
`hormone
`
`MSH; melanotropin,
`intermedin
`
`expands melanophores (changes skin
`color); no known function in humans
`
`by the intermediate lobe. One wonders
`if there is any significance to the fact
`that inhibitory hormones exist for the
`hormones whose target organ is not
`another endocrine gland.
`A rather different arrangement ex-
`ists for the neurohypophysis. The neu-
`rons in the fiber tracts that run from
`the hypothalamus to the posterior lobe
`release substances from their terminals
`upon stimulation, but the nerve end-
`ings are near capillaries in the posterior
`lobe. These capillaries are not part of
`the hypophyseal portal system, and the
`substances entering them are carried
`throughout the body. The hormones of
`the posterior pituitary are actually pro-
`duced by neurons whose cell bodies are
`in the hypothalamus. Since so-called
`posterior lobe hormones are released
`from it, but not produced by it, one
`may rightfully question whether the
`posterior lobe is, in fact, an endocrine
`gland.
`The arrangement by which the
`hypothalamus exerts control over the
`
`pituitary gland is not as unique as it
`might seem. We have seen that all
`nerve fibers produce their actions by
`releasing a chemical, which we call a
`transmitter, from their terminals when
`they are stimulated. The hypothalamic
`neurons do the same. The difference is
`that they release their ”transmitter sub-
`stances” near capillaries instead of post-
`jurictional membranes. In the posteri-
`or lobe the substances are released near
`and enter capillaries of the general cir-
`culation of distribution throughout the
`body;
`the substances are called hor-
`mones. Other hypothalamic fibers re-
`lease their ”transmitter” near capillar-
`ies of the hypophyseal portal system to
`be carried to the anterior and interme-
`diate lobes where they diffuse into the
`interstitial fluid and act on the pituitary
`cells; these substances are called releas-
`ing hormones. Each kind of releasing
`hormone ”recognizes” the cell
`that
`produces ”its” hormone because the
`membrane of
`that cell has receptor
`binding sites for that releasing hor-
`
`

`
`The Pituitary Gland and Hormone Control
`361
`
`
`
`
`
`Hypothalamus
`
`Portal vessels
`
`1)
`
`Thyrold hormone
`
`T
`
`:11.
`
`. lwwm
`
`O2 consumptlon by body cells
`
`Thyroid gland
`
`Control of hormone
`FIGURE 13-5
`secretion by hypothalamic releasing
`hormones.
`
`ried from here to there. They exert their
`action at some distant target organ.
`the
`The nervous system has all
`required elements of a control system.
`It has a well-developed efferent system.
`It can get messages to all sorts of effec-
`tors (excitable cells) to produce a re-
`sponse that may be brief and instant or
`continuous, precise and localized, or
`generalized and widespread. The ner-
`vous system has a well-developed array
`of monitors and sensors, which in-
`cludes receptors on the body surface
`that provide information about the ex-
`ternal environment, and receptors in
`skeletal muscle and viscera that
`tell
`
`about conditions inside the body. The
`nervous system has marvelous centers
`to integrate all this information and to
`send out directions. The centers are
`
`organized in a hierarchy of command
`with the minimal elements for a simple
`response (a stretch reflex) on the spinal
`cord level. Centers in the brainstem
`exert control over the cord centers, and
`centers above that
`(cerebellum, basal
`ganglia) exert a higher level of control,
`while areas of the cerebral cortex exert
`control over all of those below.
`
`The endocrine system, on the other
`
`mone. The releasing hormone then
`binds to it and triggers the sequence of
`events
`for which that
`cell
`is pro-
`grammed. The hormone produced as a
`result is released from the pituitary cell,
`enters the bloodstream, and is carried
`to the target organs.
`Hypothalamic control of pituitary
`function is the means by which the
`nervous
`system exerts control over
`many hormonal systems. The nervous
`system has a much more highly devel-
`oped sensing mechanism, and the hy-
`pothalamus, in a sense, gives the endo-
`crine system a ”digest” of the sensory
`information obtained by the nervous
`system. This information ensures that
`endocrine responses are appropriate to
`internal and external conditions. The
`
`hypothalamic connections explain the
`effects of stresses (emotional and other-
`wise) upon a number of hormonally
`controlled processes.
`
`Neural Versus Hormonal
`Control
`
`Most of the activities of the body
`are in response to a stimulus, with
`controls built into the system to ensure
`its effectiveness. A control system for
`stimulus-response behavior
`requires
`the following elements:
`
`1 A mechanism to produce a
`response (the efferent and effector).
`2 A mechanism to detect or m