Textbook of Endocrine Physiology
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Textbook of Endocrine
Physiology
SIXTH EDITION
EDITED BY
W I L L I A M J . K O VA C S , M D
Professor of Medicine
The Pennsylvania State University
College of Medicine
Hershey, Pennsylvania
SERGIO R. OJEDA, DVM
Senior Scientist and Head
Division of Neuroscience
Oregon National Primate Research Center
Beaverton, Oregon
1
1
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Library of Congress Cataloging-in-Publication Data
Textbook of endocrine physiology / edited by William J. Kovacs, Sergio R. Ojeda. – 6th ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-19-974412-1
1. Endocrine glands–Physiology. 2. Endocrinology. I. Kovacs, William J. II. Ojeda, Sergio R.
[DNLM: 1. Endocrine Glands–physiology. 2. Hormones–physiology. WK 102]
QP187.T43 2012
612.4–dc22 2011012551
___________________________________
Cover image: Schematic representation of some hormone receptors that transmit hormonal signals
from the cell surface to the interior. From left to right are shown receptors for Epidermal Growth Factor,
Insulin (with two identical chains), Platelet Derived Growth Factor, Growth Hormone, and Atrial
Natriuretic Peptide.
9 8 7 6 5 4 3 2 1
Printed in the United States of America
on acid-free paper
Preface
With this edition, the Textbook of Endocrine Physiology acquires one new editor,
ten new authors, and a variety of changes in style and layout. Our aim, how-
ever, remains unchanged from previous editions: to provide a clear and concise
presentation of the basics of endocrine physiology, emphasizing the contribu-
tions of biological science while utilizing clinical insights as tools to enhance
understanding of normal physiologic processes. Our hope is that this approach
continues to serve students who will pursue careers in basic or clinical investi-
gation as well as those who study endocrine physiology as a foundation for work
in the care of persons with endocrine disorders. We believe that a comprehensive
grounding in physiology is fundamental to either career pursuit and we hope to
contribute to that knowledge base.
We owe a debt of gratitude to Dr. James E. Griffin, who shepherded the text-
book through its first five editions over the past two decades. His editorial skills
and personal commitment to the undertaking set the benchmarks toward which
we strive. We wish Jim well in his retirement.
Sadly, one of our contributing authors is no longer with us. Dr. Keith L. Parker,
our colleague, died in December 2008, and the editors and authors dedicate this
volume to his memory. Keith served as the J. D. and Maggie E. Wilson Distinguished
Professor in Biomedical Research and Chief of the Division of Endocrinology and
Metabolism at the University of Texas Southwestern Medical Center, the home
institution of many of our authors, and certainly the “home” of this book. Keith
built on the Southwestern tradition of excellence in endocrinology. He believed
that the most rigorous science was the best tool for expanding human knowledge
and for informing the practice of clinical medicine. He explored, he taught, and he
cared for patients. He worked very hard at all those pursuits and he encouraged
others to do the same. Keith was a wonderful leader and friend, and his absence
remains keenly felt.
Our book is intended to serve principally as an introduction to endocrine phys-
iology for those just beginning their medical or graduate education. Keith’s
approach to life in science would be a good introduction for them, too. He asked
v
vi PREFACE
important questions, interacted with the worldwide research community in a
collegial way, and pursued all his work with a joy that came from the recognition
that it is a great privilege to be a learner and a teacher. We should all do it
that way.
For all the students and teachers in endocrinology we offer our new edition
of this little book in the hope that it serves the needs of all and encourages some
to dig deeper and create the discoveries that will fill the pages of editions to
come.
We express our deepest appreciation to our editors at the Oxford University
Press, Staci Hou and Andrea Seils.
Hershey, PA W.J.K.
Beaverton, OR S.R.O.
Keith L. Parker, MD, PhD
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Contents
Contributors xi
1. Organization of the Endocrine System 3
2. Genes and Hormones 21
3. Mechanisms of Hormone Action 58
4. Assessment of Endocrine Function 99
5. The Anterior Pituitary and Hypothalamus 116
6. The Posterior Pituitary and Water Metabolism 148
7. Sexual Differentiation 172
8. Female Reproductive Function 194
9. Male Reproductive Function 239
10. Fertilization, Implantation,
and Endocrinology of Pregnancy 264
11. Growth Regulation 292
12. The Thyroid 311
X CONTENTS
13. The Adrenal Glands 346
14. Calcium Homeostasis 381
15. Glucose, Lipid, and Protein Metabolism 411
Index 441
Contributors
Richard J. Auchus, MD, PhD Daniel W. Foster, MD
Professor of Medicine Professor of Internal Medicine
University of Michigan Medical School University of Texas Southwestern
Ann Arbor, Michigan Medical Center
Dallas, Texas
Victor E. Beshay, MD
Assistant Professor of Obstetrics Hans K. Ghayee, DO
and Gynecology Assistant Professor of Internal
University of Texas Southwestern Medicine
Medical Center University of Texas Southwestern
Dallas, Texas Medical Center
Dallas, Texas
Bruce R. Carr, MD
Professor of Obstetrics Stephen R. Hammes, MD, PhD
and Gynecology Professor of Medicine
University of Texas Southwestern University of Rochester School
Medical Center of Medicine and Dentistry
Dallas, Texas Rochester, New York
Gregory O. Clark, MD Sumitha S. Hathiramani, MD
Assistant Professor of Internal Assistant Professor of Internal
Medicine Medicine
University of Texas Southwestern University of Texas Southwestern
Medical Center Medical Center
Dallas, Texas Dallas, Texas
xi
xii C O N T R I B U TO R S
Shelby A. Holt, MD Sergio R. Ojeda, DVM
Associate Professor of Surgery Senior Scientist and Head
University of Texas Southwestern Division of Neuroscience
Medical Center Oregon National Primate
Dallas, Texas Research Center
Beaverton, Oregon
Jyotsna Keni, MD
Pediatric Endocrinology Keith L. Parker, MD, PhD
Kaiser Permanente (deceased)
Bakersfield, CA Professor of Internal Medicine
University of Texas Southwestern
William J. Kovacs, MD Medical Center
Professor of Medicine Dallas, Texas
The Pennsylvania State University-
College of Medicine Anna Pawlikowska-Haddal,
Hershey, Pennsylvania MD, PhD
Associate Professor of Pediatrics
Ildiko Lingvay, MD, MPH, MSCS University of California, Los Angeles
Assistant Professor of Internal Los Angeles, California
Medicine
University of Texas Southwestern William E. Rainey, PhD
Medical Center Regents Professor of Physiology
Dallas, Texas Medical College of Georgia
Augusta, Georgia
Naim M. Maalouf, MD
Assistant Professor of Internal Willis K. Samson, PhD, DSc
Medicine Professor of Pharmacological and
University of Texas Southwestern Physiological Science
Medical Center Saint Louis University School
Dallas, Texas of Medicine
St. Louis, Missouri
Michael J. McPhaul, MD
Professor of Internal Medicine Perrin C. White, MD
University of Texas Southwestern Professor of Pediatrics
Medical Center University of Texas Southwestern
Dallas, Texas Medical Center
Dallas, Texas
Carole R. Mendelson, PhD
Professor of Biochemistry and
Obstetrics & Gynecology
University of Texas Southwestern
Medical Center
Dallas, Texas
Textbook of Endocrine
Physiology
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1
Organization of the Endocrine System
S E R G IO R . O J E DA A N D W I L L I A M J . KO VAC S
Multicellular organisms are endowed with coordinating systems that regulate and
integrate the function of the different cells composing these organisms. Two main
interacting systems perform this critical function: the nervous system and the
endocrine system. The former employs electrochemical signals to convey regula-
tory inputs to peripheral organs and to receive information from them; the latter
produces chemical agents that, in general, are transported systemically by the
bloodstream to the target organs.
The two systems are closely interconnected. The most conspicuous connection
is that of the hypothalamus and the pituitary gland. Hypothalamic neurosecre-
tory cells produce substances that are delivered to the portal blood vessels (see
Chapter 5) and transported to the anterior pituitary (adenohypophysis), where
they regulate the secretion of adenohypophyseal hormones. Other hypothalamic
neurons send their axons to the posterior pituitary, from which they release their
neurosecretory products directly into the bloodstream. The nervous system also
innervates most, if not all, endocrine glands, including the gonads, the thyroid,
and the adrenals. The nerves control not only blood flow but also the secretion of
hormones. In turn, the endocrine system regulates the function of the nervous
system. For example, gonadal and adrenocortical hormones act directly on the
central nervous system to either inhibit or to stimulate the secretion of neuro-
peptides involved in the control of the pituitary-gonadal and pituitary-adrenal
axes, respectively (i.e., gonadotrophin-releasing hormone [GnRH], also known
as luteinizing hormone-releasing hormone [LHRH], and corticotropin-releasing
hormone [CRH]; see Chapter 5).
Although conventional definitions of the nervous and endocrine systems
emphasize their differences, the two systems also display similarities. For instance,
the nervous system produces not only substances that act across synapses, but
it also releases signaling molecules that reach distant target cells via the blood-
stream. Among these substances of neural origin are the hypothalamic-releasing
hormones that control the secretion of anterior pituitary hormones; epinephrine
of adrenomedullary origin, which upon release into the bloodstream can affect
3
4 TEXTBOOK OF ENDOCRINE PHYSIOLOGY
the function of various organs, such as the liver and muscle; and oxytocin
and vasopressin, which are secreted by hypothalamic neurons and act on the
mammary gland and uterus (oxytocin) to stimulate the activity of contractile
tissue and on the kidney (vasopressin) to regulate extracellular fluid volume.
Conversely, several peptides originally discovered in the gastrointestinal tract,
where they exert hormonal actions, are produced in neurons of both the central
and peripheral nervous systems, where they appear to act as neurotransmitters
or neuromodulators. Examples of these hormones are gastrin, secretin, ghrelin,
and vasoactive intestinal peptide.
Because of their interrelationships, endocrine glands and the components
of the nervous system that regulate endocrine function are referred to as the
neuroendocrine system. The discipline devoted to the study of this system is called
neuroendocrinology (see Chapter 5). It is now clear that the neuroendocrine system
does not operate alone; instead, it is subjected to regulatory input from a seem-
ingly unrelated source, the immune system. The relationship between the neu-
roendocrine system and the immune system is reciprocal: hormones influence
the immune system, and cytokines (the secretory products of the immune system)
affect neuroendocrine functions. Cells of the immune system have been found
to secrete certain hormones such as adrenocorticotropin (ACTH), β -endorphin,
prolactin, and GnRH, which until recently were thought to be produced only in
the brain and/or the pituitary gland.
Perhaps the best-characterized neuroendocrine–immune system relationship
is that of the immune-hypothalamic-pituitary-adrenal axis. Cytokines, particu-
larly interleukin-1 (produced by activated macrophages), enhance CRH secretion
from the hypothalamus. In turn, CRH stimulates the pituitary gland to secrete
ACTH. This hormone acts on the adrenal cortex to elicit glucocorticoid secretion.
Glucocorticoids then exert immunomodulatory effects on neutrophils, mono-
cytes, and lymphocytes.
The immune system also affects the secretion of other pituitary hormones via
the hypothalamus. In addition to the stimulatory effect of interleukin-1 on CRH
release, cytokines have been shown to depress thyrotropin-releasing hormone
(TRH) and GnRH production. In turn, several pituitary hormones and neuroen-
docrine peptides, including somatostatin, thyroid-stimulating hormone (TSH),
and growth hormone (GH), are able to affect specific immunological functions
(such as immunoglobulin synthesis, which is enhanced by TSH, and lymphocyte
production, which is increased by GH).
The ovary provides another example of the interrelationships between the
endocrine and the immune systems. Cytokines directly regulate certain ovarian
functions, and ovarian hormones affect the immune system. For instance, inter-
leukin-1 synthesis increases in the ovary during the hours preceding ovulation,
resulting in a greater production of progesterone and prostaglandins, which in
turn are required for ovulatory rupture. Conversely, low doses of progesterone
enhance the expression of the interleukin-1 gene in macrophages.
Organization of the Endocrine System 5
In their definition of a hormone, Baylis and Starling specified that for a sub-
stance to be considered a hormone, it should meet the requirement of being pro-
duced by an organ in small amounts, released into the bloodstream, and
transported to a distant organ to exert its specific actions. This definition applies
to most of the classical hormones produced by the endocrine glands. However, hor-
mones can act on:
• Contiguous cells, performing a paracrine function
• The same cells that produce them, performing an autocrine function
• On other cells in a nondiffusible, juxtacrine manner. This is a cell-cell commu-
nication pathway used by some nonclassical hormones, such as growth factors
of the epidermal growth factor (EGF) family of trophic polypeptides. It is
established when a membrane-anchored growth factor precursor on one cell is
cleaved to yield the mature form of the growth factor, which then interacts
with its membrane-bound receptor located on an adjacent cell.
Recent studies have unveiled a new form of hormone-like, cell-cell communication
performed by vesicular structures known as “exosomes.” These structures result
from the fusion of intracellular multivesicular bodies with the plasma membrane,
followed by extracellular release of their microvesicle (exosome) content. Exosomes
contain both membrane-associated and cytosolic proteins; surprisingly, they are
enriched in RNA and microRNAs, which they can transfer to other (neighboring)
cells. Exosomes have been shown to be involved in several functions, including
transport of infectious agents, immune surveillance, coagulation, and tumor pro-
gression. An intriguing new finding is that exosomes can influence functions of
distant cells. Exosomes derived from adipose tissue have been shown to cause
insulin resistance, an effect they appear to exert by facilitating conversion
of blood monocytes into activated macrophages, which then induce insulin resis-
tance on distant tissues via production of certain cytokines, such as tumor necro-
sis factor alpha.
Endocrine Glands and Hormones
The endocrine system is composed of several glands that, located in different
regions of the body, produce hormones with different functions. Endocrine glands
are ductless; that is, they release their secretory products directly into the blood-
stream and not into a duct system. Because they are richly vascularized, each
secreting cell can deliver its products efficiently into the circulation.
The classical endocrine glands and their known secretory products are listed in
Table 1-1. This list includes recognized hormones produced in organs that do not
have primary endocrine function. Perhaps the earliest example of this was the
recognition that hormones are produced by cells scattered along the mucosa of
6 TEXTBOOK OF ENDOCRINE PHYSIOLOGY
Table 1-1 Classical Endocrine Glands and Their Hormones
Gland Hormone
Pituitary Anterior lobe Luteinizing hormone (LH), follicle-stimulating
hormone (FSH), prolactin (PRL), growth hormone
(GH), adrenocorticotropin (ACTH), β-lipotropin,
β-endorphin, thyroid-stimulating hormone (TSH)
Intermediate Melanocyte-stimulating hormone (MSH), β-endorphin
lobe
Posterior lobe Vasopressin (AVP) or antidiuretic hormone (ADH),
oxytocin
Thyroid Thyroxine (T4), 3,5,3’-triiodothyronine (T3), calcitonin
Parathyroid Parathyroid hormone (PTH)
Adrenal Cortex Cortisol, aldosterone, dehydroepiandrosterone,
androstenedione
Medulla Epinephrine, norepinephrine
Gonads Testis Testosterone, estradiol, androstenedione, inhibin,
activin, müllerian-inhibiting substance
Ovary Estradiol, progesterone, testosterone,
androstenedione, inhibin, activin, FSH-releasing
peptide, relaxin, follistatin
Placenta Human chorionic gonadotropin (hCG), human
placental lactogen (hPL), progesterone, estrogen
Pancreas Insulin, glucagon, somatostatin, pancreatic
polypeptide, gastrin, vasoactive intestinal peptide (VIP)
Pineal Melatonin, biogenic amines, several peptides
the stomach and small intestine. The brain, heart, kidney, liver, and certain blood
elements also produce peptides or form active steroid metabolites from circulat-
ing precursors that deserve the designation of hormones (Table 1-2). Not all of
these hormones will be considered in this textbook.
Chemical Nature of Hormones
Chemically, the hormones fall into three general categories:
• Hormones derived from single amino acids. They are the amines, such as nore-
pinephrine, epinephrine, and dopamine, which derive from the amino acid
Organization of the Endocrine System 7
Table 1-2 Nonclassical “Endocrine Organs” and Their Hormones
Organ Hormone
Brain (especially hypothalamus) Corticotropin-releasing hormone (CRH),
thyrotropin-releasing hormone (TRH),
gonadotropin hormone–releasing
hormone (GnRH), RFamide-related peptides,
growth hormone–releasing hormone (GHRH),
somatostatin, growth factors [fibroblast growth
factors, transforming growth factor-alpha (TGF-α),
transforming growth factor-beta (TGF-β), insulin-
like growth factor I (IGF-I)]
Heart Atrial natriuretic peptides
Kidney Erythropoietin, renin, 1,25-dihydroxyvitamin D
Liver, other organs, fibroblasts IGF-I
Adipose tissue Leptin, adiponectin, tumor necrosis factor-alpha
(TNFα), interleukin 6 (IL-6)
Gastrointestinal tract Cholecystokinin (CCK), gastrin, ghrelin, secretin,
vasoactive intestinal peptide (VIP), enteroglucagon,
gastrin-releasing peptide
Platelets Platelet-derived growth factor (PDGF), TGF-β
Macrophages, lymphocytes aCytokines,TGF-β, pro-opiomelanocortin (POMC)-
derived peptides, TNFα
Various sites aEpidermal growth factor (EGF), TGF-α,
neuregulins, neurotrophins
aNot considered to be hormones, but they can act as such.
tyrosine, and the thyroid hormones, 3,5,3’-triiodothyronine (T3) and
3,5,3’,5’-tetraiodothyronine (thyroxine, T4), which derive from the combina-
tion of two iodinated tyrosine amino acid residues.
• Peptides and proteins. These can be as small as TRH (three amino acids) and
as large and complex as GH and follicle-stimulating hormone (FSH), which
have about 200 amino acid residues and molecular weights in the range of
25,000–30,000 daltons.
• Steroid hormones, which are derivatives of cholesterol and can be grouped into
two types: (1) those with an intact steroid nucleus such as the gonadal and
adrenal steroids and (2) those with a broken steroid nucleus (the B ring), such
as vitamin D and its metabolites. Figure 1-1 provides examples of these three
categories of hormones.
8 TEXTBOOK OF ENDOCRINE PHYSIOLOGY
Amines Thyroid Hormones
OH I I NH2
HO CH CH2 NH2 HO O CH2 CH COOH
O
HO (Norepinephrine) I
(3,5,3'-triiodothyronine, T3)
Polypeptides Proteins
1
H2N
Gly NH2
140
Cys
Cys Pro Leu
Tyr
180
Asn
Ile
Gln 190 COOH
165
70
55
(Oxytocin) (Growth hormone)
Steroids
CH2OH
C O
HO OH
O
OH
(Cortisol) (Vitamin D3)
Figure 1-1 Examples of different categories of hormones. In the case of a protein
hormone, each circle represents an amino acid, as shown for the polypeptide hormone
depicted in the figure.
Function of Hormones
Regardless of their chemical nature, hormones are present in the bloodstream in
very low concentrations (10-7 to 10-12 M). Thus, it is not surprising that a prereq-
uisite for any hormone to exert its actions is that it must first bind to specific
high-affinity cellular receptors. These receptors may be located on the cell mem-
brane, as in the case of protein hormones and amines, or in the nucleus, as with
thyroid and steroid hormones (see Chapter 3). Another characteristic feature of
hormones is that a single hormone can exert various effects in different tissues;
conversely, several hormones can regulate a single function.
• Single hormone acting on different tissues: Estradiol exemplifies the versatility of
these hormones. It is produced by the ovary and can act on the ovarian follicles
Organization of the Endocrine System 9
themselves to promote granulosa cell differentiation, on the uterus to stimu-
late its growth and maintain the cyclic change of the uterine mucosa, on the
mammary gland to simulate ductal growth, on bone to promote linear growth
and closure of the epiphyseal plates, on the hypothalamic-pituitary system to
regulate the secretion of gonadotropins and prolactin, and on general meta-
bolic processes to affect adipose tissue distribution, volume of extracellular
fluid, and so on. In each case, estradiol acts through the same common mecha-
nism, namely, binding to high-affinity, specific nuclear receptors followed by
attachment of the receptor-steroid complex to DNA regions of genes that are
expressed in a tissue-specific manner.
• Single function regulated by more than one hormone: An example is the release of
fatty acids (lipolysis) from adipose tissue stores. A variety of hormones, includ-
ing catecholamines, glucagon, secretin, prolactin, and β –lipotropin, stimulate
lipolysis within minutes by activating, via cyclic adenosine monophosphate
(AMP), a rate-limiting triglyceride hydrolase known as hormone-sensitive lipase.
Growth hormone and glucocorticoids also stimulate lipolysis, but only after a
time lag of 2 hours because they induce the synthesis of hormone-sensitive
lipase instead of activating the hydrolase. Other hormones such as insulin,
insulin-like growth factors (IGFs), oxytocin, and gastric-inhibitory polypep-
tide inhibit lipolysis. An example of a complex function regulated by differ-
ent hormones is the development of the mammary gland, which is under the
primary influence of prolactin, estradiol, and progesterone and the permissive
influence of glucocorticoids, thyroid hormones, and insulin. The effect of these
latter hormones is considered permissive because, by themselves, they have
little effect, but when they are present the actions of prolactin, estrogen, and
progesterone become fully manifested.
Hormones exert their functions in four broad physiological areas: reproduction,
growth and development, maintenance of the internal environment, and the
regulation of energy balance.
REPRODUCTION
Hormones produced by the gonads (androgens, estrogen, progestins) and the
anterior pituitary gland (luteinizing hormone [LH], FSH, GH, and prolactin) inter-
act to regulate the growth and structural integrity of the reproductive organs, the
production of gametes, the patterns of sexual behavior, the phenotypic difference
between the sexes, and the continuation of the species (through their effects on
ovulation, spermatogenesis, pregnancy, and lactation).
Several examples of these interactions can be provided. For instance, estradiol
induces hypertrophy and hyperplasia of both the muscular and endothelial lay-
ers of the uterine wall; in turn, the secretion of estradiol from the ovary is under
the control of pituitary gonadotropins. Testosterone, produced by specialized
10 TEXTBOOK OF ENDOCRINE PHYSIOLOGY
(Leydig) cells in the testis, is under the control of LH, and it exerts tropic effects
on sex accessory glands such as the prostate and seminal vesicles. Both estradiol
in females and testosterone in males play fundamental roles in determining
the female and male external appearance at puberty. Testosterone promotes the
growth of the testes, scrotum, and penis and stimulates muscle development, par-
ticularly that of the pectoral region and shoulders. Estradiol promotes the devel-
opment of the female external genitalia and the redistribution of adipose tissue,
which localizes more noticeably in the thighs, hips, and breasts (see Chapter 8).
Although gonadal steroids do not induce a stereotyped pattern of sexual behavior
in humans, as in animals, they are important in maintaining the libido.
Both ovulation and spermatogenesis are processes tightly controlled by the
pituitary gonadotropins LH and FSH, which act either directly on the gonads to
promote follicular development (ovary) and formation of sperm (testis) or indi-
rectly through their stimulatory effects on estrogen and testosterone secretion.
During pregnancy various hormones of placental origin, including estradiol, pro-
gesterone, chorionic gonadotropin, placental lactogen, and several others (see
Chapter 10), contribute to maintaining the normal progression of pregnancy. After
delivery, another group of hormones, most noticeably prolactin (see earlier), main-
tains the structure and function of the lactating breast.
GROWTH AND DEVELOPMENT
Various hormones play primary and permissive roles in the timing and progres-
sion of growth, both for overall body size and for individual tissues. In many cases
the local production of growth factors is a result of hormone action. In other
instances the production of a growth factor may be hormone independent, but
the growth factor interacts with hormones to promote or reduce growth.
The classical hormones involved in regulating growth are GH, thyroid hor-
mones, insulin, glucocorticoids, androgens, and estrogens. The stimulatory effect
of GH on bodily growth is mediated by a family of peptides known collectively as
insulin-like growth factors (IGFs; see Chapter 11). IGFs may also contribute to
mediating the stimulatory effect of androgens and estrogens on linear growth
and acquisition of muscle mass. An example of a hormone that plays both permis-
sive and primary roles in growth is T4. In its absence, GH fails to stimulate skel-
etal growth, a phenomenon that appears to be related to a reduced ability of the
tissue to respond to IGFs. In the central nervous system, however, T4 plays a pri-
mary role in inducing growth and cellular differentiation. Some of its actions in
the brain appear to be mediated by the production of a tissue-specific growth
factor, nerve growth factor (NGF). Specific hormones (GH, T4, sex steroids) can
also regulate the synthesis of peptide growth factors such as the IGFs, NGF, and
EGF. A more detailed discussion of the hormones and peptide growth factors
involved in regulating growth is presented in Chapter 11.
Organization of the Endocrine System 11
MAINTENANCE OF INTERNAL ENVIRONMENT
The maintenance of the internal environment involves the control of extracellular
fluid volume and blood pressure, the electrolyte composition of bodily fluids, the
regulation of plasma and tissue levels of calcium and phosphate ions, and the
maintenance of bone, muscle, and body stores of fat.
A multitude of hormones participates in the regulation of these processes. For
example, vasopressin or antidiuretic hormone, which is synthesized in the hypo-
thalamus and released from the posterior pituitary, acts on the kidney to induce
water reabsorption; aldosterone produced in the adrenal cortex stimulates sodium
reabsorption and potassium excretion in the kidney. Thus, both hormones con-
tribute to regulating blood pressure, extracellular fluid volume, and the electro-
lyte composition of bodily fluids.
Plasma levels of calcium and phosphate ions are controlled by parathyroid
hormone (PTH) from the parathyroid glands (see Chapter 14). The PTH increases the
serum calcium concentration mainly through its stimulatory actions on calcium
transport in bone and kidney, but also by enhancing intestinal calcium absorption
through its stimulatory influence on the renal formation of 1,25-dihydroxyvitamin D.
In addition, PTH acts on the kidney to increase phosphate excretion.
The functions of bone, muscle, and adipose tissue are regulated by hormones as
diverse as PTH, estrogens, androgens, GH, catecholamines, insulin, glucagon, and
glucocorticoids. These physiologic effects are discussed in detail in Chapters 13,
14, and 15.
R E G U L AT I O N O F E N E R G Y B A L A N C E
For an organism to survive, it must be able to convert the calories contained in
food into energy, to store part of that energy for subsequent use, and to mobilize
it when necessary. Maintenance of energy homeostasis is of paramount impor-
tance for the proper regulation of body weight, which requires a balance between
food consumption and energy expenditure. The hypothalamus plays a central role
in this process by integrating a variety of afferent sensory, visual, biochemical,
and hormonal signals reflecting the nutritional status of the organism. Processing
of these signals results in the activation of efferent signals that regulate both
feeding behavior and energy expenditure. The latter is regulated via mechanisms
controlling the metabolic rate, such as those influenced by the sympathetic
and parasympathetic nervous systems, and by insulin, glucagon, and thyroid
hormones.
Several of the afferent signals controlling energy balance are now known. For
instance, leptin, a hormone produced by white adipose tissue, has been shown to
act on the brain to decrease food intake and increase energy expenditure. Leptin
acts through specific receptors, which are particularly abundant in hypothalamic
