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The Endocrine System

An Overview

Susanne Hiller-Sturmhöfel, Ph.D., and Andrzej Bartke, Ph.D.

A plethora of hormones regulate many of the body’s functions, including growth and
development, metabolism, electrolyte balances, and reproduction. Numerous glands
throughout the body produce hormones. The hypothalamus produces several releasing and
inhibiting hormones that act on the pituitary gland, stimulating the release of pituitary
hormones. Of the pituitary hormones, several act on other glands located in various regions
of the body, whereas other pituitary hormones directly affect their target organs. Other
hormone-producing glands throughout the body include the adrenal glands, which primarily
produce cortisol; the gonads (i.e., ovaries and testes), which produce sex hormones; the
thyroid, which produces thyroid hormone; the parathyroid, which produces parathyroid
hormone; and the pancreas, which produces insulin and glucagon. Many of these hormones
are part of regulatory hormonal cascades involving a hypothalamic hormone, one or more
pituitary hormones, and one or more target gland hormones. KEY WORDS: endocrine function;
hormones; hypothalamus; pituitary gland; gonad function; thyroid; parathyroid; pancreas;
biochemical mechanism; biological feedback; biological regulation; hypothalamus-pituitary
axis; pituitary-adrenal axis; pituitary-thyroid axis; literature review

F
or the body to function properly, (i.e., within fractions of seconds) of composition of bodily fluids; and repro-
its various parts and organs must information between different body duction. This article provides an
communicate with each other to regions. Conversely, hormonal commu- overview of the hormone systems
ensure that a constant internal environ- nication, which relies on the production involved in those regulatory processes.
ment (i.e., homeostasis) is maintained. and release of hormones from various The article first summarizes some of the
For example, neither the body temper- glands and on the transport of those basic characteristics of hormone-
ature nor the levels of salts and minerals hormones via the bloodstream, is better mediated communication within the
(i.e., electrolytes) in the blood must suited for situations that require more body, then reviews the various glands
fluctuate beyond preset limits. Com- widespread and longer lasting regulatory involved in those processes and the
munication among various regions of actions. Thus, the two communication
the body also is essential for enabling systems complement each other. In SUSANNE HILLER-STURMHÖFEL, PH.D.,
the organism to respond appropriately addition, both systems interact: Stimuli is a science editor of Alcohol Health &
to any changes in the internal and from the nervous system can influence Research World.
external environments. Two systems the release of certain hormones and
help ensure communication: the nervous vice versa. ANDRZEJ BARTKE, PH.D., is professor
system and the hormonal (i.e., neuroen- Generally speaking, hormones con- and chairman of physiology at Southern
docrine) system. The nervous system trol the growth, development, and Illinois University School of Medicine,
generally allows rapid transmission metabolism of the body; the electrolyte Carbondale, Illinois.

Vol. 22, No. 3, 1998 153
major hormones they produce. For molecular structures (e.g., size and or in the cell nucleus. The hormone-
more in-depth information on those chemical properties). As a result of the receptor complexes then bind to certain
hormones, the reader should consult structural differences, their mechanisms regions of the cell’s genetic material (i.e.,
endocrinology textbooks (e.g., Con- of action (e.g., whether they can enter the DNA), thereby regulating the activ-
stanti et al. 1998; Wilson et al. 1998). their target cells and how they modulate ity of specific hormone-responsive genes.
Finally, the article presents various the activity of those cells) also differ. Amino acid derivatives are modi-
endocrine systems in which hormones Steroids, which are produced by the fied versions of some of the building
produced in several organs cooperate gonads and part of the adrenal gland blocks of proteins. The thyroid gland
to achieve the desired regulatory effects. (i.e., the adrenal cortex), have a molecular and another region of the adrenal
The discussions focus primarily on structure similar to that of cholesterol. glands (i.e., the adrenal medulla) pro-
the system responses in normal, healthy The molecules can enter their target duce this type of hormone (i.e., the
people. For information regarding cells and interact with receptors in the amino acid derivatives). Like steroids,
alcohol’s effects on some of the hormone fluid that fills the cell (i.e., the cytoplasm) amino acid derivatives can enter the
systems, the reader is referred to sub-
sequent articles in this issue of Alcohol
Health & Research World.

What Are Hormones?
Hypothalamus
Hormones are molecules that are pro-
duced by endocrine glands, including
Thyroid gland
the hypothalamus, pituitary gland, Pituitary gland
adrenal glands, gonads, (i.e., testes
and ovaries), thyroid gland, parathyroid Parathyroid gland
glands, and pancreas (see figure 1).
The term “endocrine” implies that in
response to specific stimuli, the products
of those glands are released into the
bloodstream.1 The hormones then are
carried via the blood to their target
cells. Some hormones have only a few
specific target cells, whereas other
hormones affect numerous cell types
throughout the body. The target cells
for each hormone are characterized by
the presence of certain docking mole-
cules (i.e., receptors) for the hormone Adrenal
that are located either on the cell surface gland
Pancreas
or inside the cell. The interaction (Islets of
between the hormone and its receptor Langerhans)
triggers a cascade of biochemical reac-
tions in the target cell that eventually
Ovary
modify the cell’s function or activity.
(in female)

Mechanisms of Action
Testis
Several classes of hormones exist, includ- (in male)
ing steroids, amino acid derivatives,
and polypeptides and proteins. Those
hormone classes differ in their general

1
Conversely, exocrine glands (e.g., sweat glands Figure 1 Schematic representation of the location of the major hormone-producing
and salivary glands) release their secretions to the (i.e., endocrine) organs in the body. (For the purposes of illustration, both
outside of the body (e.g., sweat) or into a hollow
male and female endocrine organs are presented here.)
space that is open to the outside (e.g., saliva
released into the mouth).

154 Alcohol Health & Research World
The Endocrine System

cell, where they interact with receptor cell surface. The interaction initiates which are transported via the blood to
proteins that are already associated biochemical changes in either the cell’s the pituitary gland. There, the releasing
with specific DNA regions. The membrane or interior, eventually mod- hormones induce the production and
interaction modifies the activity of ifying the cell’s activity or function. secretion of pituitary hormones, which
the affected genes. in turn are transported by the blood to
Polypeptide and protein hormones their target glands (e.g., the adrenal
are chains of amino acids of various
Regulation of Hormone Activity glands, gonads, or thyroid). In those
lengths (from three to several hundred To maintain the body’s homeostasis glands, the interaction of the pituitary
amino acids). These hormones are and respond appropriately to changes hormones with their respective target
found primarily in the hypothalamus, in the environment, hormone produc- cells results in the release of the hormones
pituitary gland, and pancreas. In some tion and secretion must be tightly that ultimately influence the organs
instances, they are derived from inactive controlled. To achieve this control, targeted by the hormone cascade.
precursors, or pro-hormones, which many bodily functions are regulated Constant feedback from the target
can be cleaved into one or more active not by a single hormone but by several glands to the hypothalamus and pitu-
hormones. Because of their chemical hormones that regulate each other itary gland ensures that the activity of
structure, the polypeptide and protein (see figure 2). For example, for many the hormone system involved remains
hormones cannot enter cells. Instead, hormone systems, the hypothalamus within appropriate boundaries. Thus,
they interact with receptors on the secretes so-called releasing hormones, in most cases, negative feedback mech-
anisms exist by which hormones
released by the target glands affect
the pituitary gland and/or hypo-
thalamus (see figure 2). When certain
predetermined blood levels of those
Hypothalamus
hormones are reached, the hypothala-
mus and/or the pituitary ceases
hormone release, thereby turning
off the cascade. In some instances, a
Releasing hormone so-called short-loop feedback occurs,
Short-loop
in which pituitary hormones directly
feedback act back on the hypothalamus.
The sensitivity with which these
Anterior pituitary negative feedback systems operate
(i.e., the target hormone levels that
are required to turn off hypothalamic
or pituitary hormone release) can
Pituitary hormone
change at different physiological states
or stages of life. For example, the
progressive reduction in sensitivity
Target gland of the hypothalamus and pituitary to
negative feedback by gonadal steroid
hormones plays an important role in
sexual maturation.
Although negative feedback is
more common, some hormone
Target gland hormone systems are controlled by positive
feedback mechanisms, in which a
target gland hormone acts back on
the hypothalamus and/or pituitary
Figure 2 Schematic representation of negative feedback mechanisms that control
to increase the release of hormones
endocrine system activity. In many cases, the hormones released from the
target gland act back on the pituitary and/or hypothalamus, repressing
that stimulate the secretion of the
further hormone release from both organs and thereby shutting off the target gland hormone. One such
system. For a short-loop negative feedback mechanism, pituitary hormones mechanism occurs during a woman’s
act directly back on the hypothalamus, inhibiting the release of hypothalamic menstrual period: Increasing estrogen
hormones. levels in the blood temporarily
stimulate, rather than inhibit, hormone
NOTE: + = stimulates; – = inhibits.
release from the pituitary and hypo-
thalamus, thereby further increasing

Vol. 22, No. 3, 1998 155
Hormones Produced by the Major Hormone-Producing (i.e., Endocrine) Glands and Their Primary Functions

Endocrine Gland Hormone Primary Hormone Function

Hypothalamus Corticotropin-releasing hormone (CRH) Stimulates the pituitary to release adrenocorticotropic
hormone (ACTH)

Gonadotropin-releasing hormone (GnRH) Stimulates the pituitary to release luteinizing hormone
(LH) and follicle-stimulating hormone (FSH)

Thyrotropin-releasing hormone (TRH) Stimulates the pituitary to release thyroid-stimulating
hormone (TSH)

Growth hormone-releasing hormone Stimulates the release of growth hormone (GH) from the
(GHRH) pituitary

Somatostatin Inhibits the release of GH from the pituitary

Dopamine Inhibits the release of prolactin from the pituitary

Anterior pituitary gland ACTH Stimulates the release of hormones from the adrenal cortex

LH In women, stimulates the production of sex hormones (i.e.,
estrogens) in the ovaries as well as during ovulation; in
men, stimulates testosterone production in the testes

FSH In women, stimulates follicle development; in men, stimu-
lates sperm production

TSH Stimulates the release of thyroid hormone

GH Promotes the body’s growth and development

Prolactin Controls milk production (i.e., lactation)
1
Posterior pituitary gland Vasopressin Helps control the body’s water and electrolyte levels

Oxytocin Promotes uterine contraction during labor and activates
milk ejection in nursing women

Adrenal cortex Cortisol Helps control carbohydrate, protein, and lipid metabolism;
protects against stress

Aldosterone Helps control the body’s water and electrolyte regulation

Testes Testosterone Stimulates development of the male reproductive organs,
sperm production, and protein anabolism

Ovaries Estrogen (produced by the follicle) Stimulates development of the female reproductive organs

Progesterone (produced by the Prepares uterus for pregnancy and mammary glands for
corpus luteum) lactation

Thyroid gland Thyroid hormone (i.e., thyroxine [T4] Controls metabolic processes in all cells
and triiodothyronine [T3])

Calcitonin Helps control calcium metabolism (i.e., lowers calcium
levels in the blood)

Parathyroid gland Parathyroid hormone (PTH) Helps control calcium metabolism (i.e., increases calcium
levels in the blood)

Pancreas Insulin Helps control carbohydrate metabolism (i.e., lowers blood
sugar levels)

Glucagon Helps control carbohydrate metabolism (i.e., increases
blood sugar levels)

1
These hormones are produced in the hypothalamus but stored in and released from the posterior pituitary gland.

156 Alcohol Health & Research World
The Endocrine System

estrogen levels and eventually lead- The hypothalamic hormones are consists of two parts: the anterior
ing to ovulation. Such a mechanism released into blood vessels that connect pituitary and the posterior pituitary.
requires a specific threshold level, the hypothalamus and the pituitary
however, at which the positive feed- gland (i.e., the hypothalamic-hypo-
back loop is turned off in order to physeal portal system). Because they
The Anterior Pituitary
maintain a stable system. generally promote or inhibit the release The anterior pituitary produces several
of hormones from the pituitary gland, important hormones that either stimu-
hypothalamic hormones are commonly late target glands (e.g., the adrenal
The Hypothalamus called releasing or inhibiting hormones. glands, gonads, or thyroid gland) to
and Its Hormones The major releasing and inhibiting produce target gland hormones or
hormones include the following (also directly affect target organs. The
The hypothalamus is a small region see table, p. 156): pituitary hormones include adreno-
located within the brain that controls corticotropic hormone (ACTH);
many bodily functions, including • Corticotropin-releasing hormone gonadotropins; thyroid-stimulating
eating and drinking, sexual functions (CRH), which is part of the hormone hormone (TSH), also called thyrotropin;
and behaviors, blood pressure and heart system regulating carbohydrate, pro- growth hormone (GH); and prolactin.
rate, body temperature maintenance, tein, and fat metabolism as well as The first three of those hormones—
the sleep-wake cycle, and emotional sodium and water balance in the body ACTH, gonadotropins, and TSH—
states (e.g., fear, pain, anger, and act on other glands. Thus, ACTH
pleasure). Hypothalamic hormones • Gonadotropin-releasing hormone stimulates the adrenal cortex to pro-
play pivotal roles in the regulation of (GnRH), which helps control duce corticosteroid hormones—
many of those functions. sexual and reproductive functions, primarily cortisol—as well as small
Because the hypothalamus is part of including pregnancy and lactation amounts of female and male sex hor-
the central nervous system, the hypothal- (i.e., milk production) mones. The gonadotropins comprise
amic hormones actually are produced two molecules, luteinizing hormone
by nerve cells (i.e., neurons). In addition, • Thyrotropin-releasing hormone (LH) and follicle-stimulating hormone
because signals from other neurons (TRH), which is part of the hormone (FSH). These two hormones regulate
can modulate the release of hypothal- system controlling the metabolic the production of female and male sex
amic hormones, the hypothalamus processes of all cells and which con- hormones in the ovaries and testes as
serves as the major link between the tributes to the hormonal regulation well as the production of the germ
nervous and endocrine systems. For of lactation cells—that is, the egg cells (i.e., ova)
example, the hypothalamus receives and sperm cells (i.e., spermatozoa).
information from higher brain centers • Growth hormone-releasing hor- TSH stimulates the thyroid gland to
that respond to various environmental mone (GHRH), which is an produce and release thyroid hormone.
signals. Consequently, hypothalamic essential component of the system The remaining two pituitary hormones,
function is influenced by both the promoting the organism’s growth GH and prolactin, directly affect their
external and internal environments as target organs.
well as by hormone feedback. Stimuli • Somatostatin, which also affects bone
from the external environment that and muscle growth but has the Growth Hormone. GH is the most
indirectly influence hypothalamic opposite effect as that of GHRH abundant of the pituitary hormones.
function include the light-dark cycle; As the name implies, it plays a pivotal
temperature; signals from other members • Dopamine, a substance that functions role in controlling the body’s growth
of the same species; and a wide variety primarily as a neurotransmitter but and development. For example, it
of visual, auditory, olfactory, and sensory also has some hormonal effects, stimulates the linear growth of the
stimuli. The communication between such as repressing lactation until it bones; promotes the growth of inter-
other brain areas and the hypothalamus, is needed after childbirth. nal organs, fat (i.e., adipose) tissue,
which conveys information about the connective tissue, endocrine glands,
internal environment, involves electro- and muscle; and controls the devel-
chemical signal transmission through opment of the reproductive organs.
molecules called neurotransmitters The Pituitary and Its Accordingly, the GH levels in
(e.g., aspartate, dopamine, gamma- Major Hormones the blood are highest during early
aminobutyric acid, glutamate, norepin- childhood and puberty and decline
ephrine, and serotonin). The complex The pituitary (also sometimes called thereafter. Nevertheless, even rela-
interplay of the actions of various the hypophysis) is a gland about the tively low GH levels still may be
neurotransmitters regulates the pro- size of a small marble and is located important later in life, and GH
duction and release of hormones from in the brain directly below the deficiency may contribute to some
the hypothalamus. hypothalamus. The pituitary gland symptoms of aging.

Vol. 22, No. 3, 1998 157
In addition to its growth-promoting require GH for normal development the pituitary is controlled by the con-
role, GH affects carbohydrate, pro- and puberty. (For more information on centration of sodium in the blood as well
tein, and fat (i.e., lipid) metabolism. alcohol’s effects on puberty and growth, as by blood volume and blood pressure.
Thus, GH increases the levels of the see the article by Dees and colleagues, For example, high blood pressure or
sugar glucose in the blood by reducing pp. 165–169.) increased blood volume results in the
glucose uptake by muscle cells and inhibition of AVP release. Consequently,
adipose tissue and by promoting glu- Prolactin. Together with other hor- more water is released with the urine,
cose production (i.e., gluconeogene- mones, prolactin plays a central role and both blood pressure and blood
sis) from precursor molecules in the in the development of the female breast volume are reduced. Alcohol also has
liver. (These actions are opposite to and in the initiation and maintenance been shown to inhibit AVP release.
those of the hormone insulin, which of lactation after childbirth. Prolactin’s Conversely, certain other drugs (e.g.,
is discussed in the section “The Pancreas function in men, however, is not well nicotine and morphine) increase AVP
and Its Hormones,” p. 160.) GH also understood, although excessive prolactin release, as do severe pain, fear, nausea,
enhances the uptake of amino acids release can lead to reduced sex drive (i.e., and general anesthesia, thereby result-
from the blood into cells, as well as libido) and impotence. Several factors ing in lower urine production and
their incorporation into proteins, and control prolactin release from the ante- water retention.
stimulates the breakdown of lipids in rior pituitary. For example, prolactin Oxytocin, the second hormone
adipose tissue. is released in increasing amounts in stored in the posterior pituitary, stim-
To elicit these various effects, GH response to the rise in estrogen levels ulates the contractions of the uterus
modulates the activities of numerous in the blood that occurs during preg- during childbirth. In nursing women,
target organs, including the liver, kid- nancy. In nursing women, prolactin is the hormone activates milk ejection
neys, bone, cartilage, skeletal muscle, released in response to suckling by the in response to suckling by the infant
and adipose cells. For some of these infant. Several releasing and inhibitory (i.e., the so-called let-down reflex).
effects, GH acts directly on the target factors from the hypothalamus also
cells. In other cases, however, GH acts control prolactin release. The most
indirectly by stimulating the produc- important of those factors is dopamine, The Adrenal Glands
tion of a molecule called insulin-like which has an inhibitory effect. and Their Hormones
growth factor 1 (IGF-1) in the liver Alcohol consumption by nursing
and kidneys. The blood then trans- women can influence lactation both The adrenal glands are small structures
ports IGF-1 to the target organs, through its effects on the release of located on top of the kidneys. Struct-
where it binds to specific receptors on prolactin and oxytocin (see the follow- urally, they consist of an outer layer
the cells. This interaction then may ing section) and through its effects on (i.e., the cortex) and an inner layer
lead to the increased DNA produc- the milk-producing (i.e., mammary) (i.e., the medulla). The adrenal cortex
tion and cell division that underlie glands and the composition of the milk. produces numerous hormones, primar-
the growth process. (For more information on alcohol’s effects ily corticosteroids (i.e., glucocorticoids
Two hypothalamic hormones con- on lactation, see the article by Heil and and mineralocorticoids). The cortex is
trol GH release: (1) GHRH, which Subramanian, pp. 178–184.) also the source of small amounts of
stimulates GH release, and (2) somato- sex hormones; those amounts, however,
statin, which inhibits GH release. This are insignificant compared with the
regulatory mechanism also involves a
The Posterior Pituitary amounts normally produced by the
short-loop feedback component, by The posterior pituitary does not ovaries and testes. The adrenal medulla
which GH acts on the hypothalamus produce its own hormones; instead, generates two substances—adrenaline
to stimulate somatostatin release. In it stores two hormones—vasopressin and noradrenaline—that are released
addition, GH release is enhanced by and oxytocin—that are produced as part of the fight-or-flight response
stress, such as low blood sugar levels by neurons in the hypothalamus. to various stress factors.
(i.e., hypoglycemia) or severe exercise, Both hormones collect at the ends The primary glucocorticoid in
and by the onset of deep sleep. of the neurons, which are located humans is cortisol (also called hydro-
Acute and chronic alcohol consump- in the hypothalamus and extend to cortisone), which helps control carbo-
tion have been shown to reduce the levels the posterior pituitary. hydrate, protein, and lipid metabolism.
of GH and IGF-1 in the blood. Both Vasopressin, also called arginine vaso- For example, cortisol increases glucose
effects have been observed in animals as pressin (AVP), plays an important role levels in the blood by stimulating glu-
well as in humans. Acute alcohol admin- in the body’s water and electrolyte econ- coneogenesis in the liver and promotes
istration also reduces GH secretion in omy. Thus, AVP release promotes the the formation of glycogen (i.e., a mole-
response to other stimuli that normally reabsorption of water from the urine cule that serves as the storage form of
enhance the hormone’s release. Those in the kidneys. Through this mech- glucose) in the liver. Cortisol also reduces
deleterious effects of alcohol may be anism, the body reduces urine volume glucose uptake into muscle and adipose
particularly harmful to adolescents, who and conserves water. AVP release from tissue, thereby opposing the effects of

158 Alcohol Health & Research World
The Endocrine System

insulin. Furthermore, in various tissues, testes). Second, the gonads synthesize of estrogens include regulating the
cortisol promotes protein and lipid steroid sex hormones that are necessary menstrual cycle, contributing to the
breakdown into products (i.e., amino for the development and function of hormonal regulation of pregnancy and
acids and glycerol, respectively) that can both female and male reproductive lactation, and maintaining female libido.
be used for gluconeogenesis. organs and secondary sex characteris- (For more information on the menstrual
In addition to those metabolic activ- tics (e.g., the adult distribution of cycle and alcohol’s effects on it, see the
ities, cortisol appears to protect the body hair, such as facial hair in men) article by Dees and colleagues, pp. 165–
body against the deleterious effects of as well as for pregnancy, childbirth, 169. For more information on alcohol’s
various stress factors, including acute and lactation. Three types of sex effects on the developing fetus, see the
trauma, major surgery, severe infections, hormones exist; each with different article by Gabriel and colleagues, pp.
pain, blood loss, hypoglycemia, and functions: (1) estrogens (e.g., estradiol), 170–177.)
emotional stress. All of these stress which exert feminizing effects; (2) During menopause, estrogen pro-
factors lead to drastic increases in the progestogens (e.g., progesterone), duction in the ovaries ceases. The result-
cortisol levels in the blood. For people which affect the uterus in preparation ing reduction in estrogen levels leads to
in whom cortisol levels cannot increase for and during pregnancy; and (3) symptoms such as hot flashes, sweating,
(e.g., because they had their adrenal androgens (e.g., testosterone), which pounding of the heart (i.e., palpitations),
glands removed), even mild stress exert masculinizing effects. In addition increased irritability, anxiety, depression,
can be fatal. Finally, high doses of to the reproductive functions, sex and brittle bones (i.e., osteoporosis). The
cortisol and other corticosteroids can hormones play numerous essential administration of estrogens (i.e., hormone
be used medically to suppress tissue roles throughout the body. For exam- replacement therapy) can alleviate those
inflammation in response to injuries ple, they affect the metabolism of symptoms and reduce the risk of osteo-
and to reduce the immune response carbohydrates and lipids, the cardio- porosis and coronary heart disease in
to foreign molecules. vascular system, and bone growth postmenopausal women. At the same
The primary mineralocorticoid in and development. time, however, hormone replacement
humans is aldosterone, which also therapy may increase the risk of certain
helps regulate the body’s water and types of cancer (e.g., breast cancer and
electrolyte balance. Its principal func-
Estrogens uterine [i.e., endometrial] cancer).
tions are to conserve sodium and to The major estrogen is estradiol, which, Alcohol consumption has been shown
excrete potassium from the body. For in addition to small amounts of estrone to increase estrogen levels in the blood
example, aldosterone promotes the and estriol, is produced primarily in and urine, even in premenopausal
reabsorption of sodium in the kidney, the ovaries. Other production sites of women who drink two drinks or less
thereby reducing water excretion and estrogens include the corpus luteum,2 per day (Reichman et al. 1993) and in
increasing blood volume. Similarly, aldo- the placenta, and the adrenal glands. postmenopausal women who drink less
sterone decreases the ratio of sodium In men and postmenopausal women, than one drink per day (Gavaler and
to potassium concentrations in sweat most estrogens present in the circula- Van Thiel 1992). These findings suggest
and saliva, thereby preventing sodium tion are derived from the conversion that moderate alcohol consumption may
loss via those routes. The effect can be of testicular, adrenal, and ovarian help prevent osteoporosis and coronary
highly beneficial in hot climates, where androgens. The conversion occurs in heart disease in postmenopausal women.
much sweating occurs. peripheral tissues, primarily adipose Other studies, however, have detected
In contrast to the glucocorticoids, tissue and skin. no consistent association between alc-
pituitary, or hypothalamic, hormones The main role of estrogens is to coor- hol consumption and increased estrogen
do not regulate aldosterone release. dinate the normal development and levels (Dorgan et al. 1994; Purohit 1998).
Instead, it is controlled primarily by functioning of the female genitalia and (For more information on the effects of
another hormone system, the renin- breasts. During puberty, estrogens pro- alcohol on postmenopausal women, see
angiotensin system, which also controls mote the growth of the uterus, breasts, the articles by Longnecker and Tseng,
kidney function. In addition, the levels and vagina; determine the pattern of pp. 185–189, and Gavaler, pp. 220–227.)
of sodium and potassium in the blood fat deposition and distribution in the
influence aldosterone levels. body that results in the typical female
shape; regulate the pubertal growth
Progestogens
spurt and cessation of growth at adult The ovaries produce progestogens dur-
The Gonads and Their height; and control the development ing a certain phase of the menstrual
Hormones of secondary sexual characteristics. In cycle and in the placenta for most of
adult women, the primary functions pregnancy. Progestogens cause changes
The gonads (i.e., the ovaries and testes) in the uterine lining in preparation
serve two major functions. First, they 2
The corpus luteum is a group of cells derived
for pregnancy and—together with
produce the germ cells (i.e., ova in from the follicle that releases the ovum during a estrogens—stimulate the development
the ovaries and spermatozoa in the particular menstrual cycle. of the mammary glands in the breasts

Vol. 22, No. 3, 1998 159
in preparation for lactation. The pri- are iodinated derivatives of the amino an adequate supply of calcium, which is
mary progestogen is progesterone. acid tyrosine. Both hormones are collec- needed for numerous functions through-
tively referred to as “thyroid hormone.” out the body (e.g., muscle movement
T4 constitutes approximately 90 percent and signal transmission within cells).
Androgens of the hormone produced in the thyroid Specifically, PTH causes reabsorption
The principal androgenic steroid is tes- gland. However, T3 is a much more of calcium from and excretion of phos-
tosterone, which is secreted primarily active hormone, and most of the T4 phate in the urine. PTH also promotes
from the testes but also, in small produced by the thyroid is converted the release of stored calcium from the
amounts, from the adrenal glands (both into T3 in the liver and kidneys. bones as well as bone resorption, both
in men and women) and from the Thyroid hormone in general serves to of which increase calcium levels in the
ovaries. Its main function is to stimulate increase the metabolism of almost all body blood. Finally, PTH stimulates the
the development and growth of the male tissues. For example, thyroid hormone absorption of calcium from the food
genital tract. In addition, testosterone stimulates the production of certain pro- in the gastrointestinal tract. Consistent
has strong protein anabolic activities— teins involved in heat generation in the with PTH’s central role in calcium meta-
that is, it promotes protein generation, body, a function that is essential for main- bolism, the release of this hormone is
which leads to increased muscle mass. taining body temperature in cold climates. not controlled by pituitary hormones
The specific functions of testosterone Moreover, thyroid hormone promotes but by the calcium levels in the blood.
vary during different developmental several other metabolic processes involv- Thus, low calcium levels stimulate PTH
stages, as follows: ing carbohydrates, proteins, and lipids release, whereas high calcium levels
that help generate the energy required suppress it.
• In the fetus, testosterone primarily for the body’s functions. In addition to Many of the functions of PTH require
ensures the development of the those metabolic effects, thyroid hormone or are facilitated by a substance called
internal and external male genitalia plays an essential role in the development 1,25-dihydroxycholecalciferol, a deriva-
of the central nervous system during late tive of vitamin D. In addition, numerous
• During puberty, testosterone pro- fetal and early postnatal developmental other hormones are involved in regulat-
motes the growth of the male sex stages. Furthermore, thyroid hormone ing the body’s calcium levels and bone
organs and is responsible for other exerts an effect similar to that of GH on metabolism, including estrogens, glu-
male developmental characteristics, normal bone growth and maturation. cocorticoids, and growth hormone. (For
such as the pubertal growth spurt Finally, thyroid hormone is required for more information on the hormonal
and eventual cessation of growth at the normal development of teeth, skin, control of bone and calcium metabolism
adult height; deepening of the voice; and hair follicles as well as for the func- and on alcohol’s effects on those systems,
growth of facial, pubic, axillary, and tioning of the nervous, cardiovascular, see the article by Sampson, pp. 190–194.)
body hair; and increase in muscular- and gastrointestinal systems.
ity and strength In addition to thyroid hormone, cer-
tain cells (i.e., parafollicular C cells) in The Pancreas and Its
• In the adult male, testosterone pri- the thyroid gland produce calcitonin, a Hormones
marily serves to maintain masculinity, hormone that helps maintain normal
libido, and sexual potency as well as calcium levels in the blood. Specifically, The pancreas is located in the abdomen,
regulate sperm production. Testos- calcitonin lowers calcium levels in the behind the stomach, and serves two
terone levels decline slightly with blood by reducing the release of calcium distinctly different functions. First, it
age, although the drop is not as dras- from the bones; inhibiting the constant acts as an exocrine organ, because the
tic as the reduction in estrogen levels erosion of bones (i.e., bone resorption), majority of pancreatic cells produce
in women during menopause. (For which also releases calcium; and inhibiting various digestive enzymes that are
information on alcohol’s effects on the reabsorption of calcium in the kidneys. secreted into the gut and which are
male reproduction, see the article by Those effects are opposite to those of essential for the effective digestion of
Emanuele and Emanuele, pp.195–201.) parathyroid hormone (PTH), which is food. Second, the pancreas serves as an
discussed in the following section. endocrine organ, because certain cell
clusters (i.e., the Islets of Langerhans)
The Thyroid and Its produce two hormones—insulin and
Hormones The Parathyroid Glands glucagon—that are released into the
and Their Hormones blood and play pivotal roles in blood
The thyroid gland, which consists of two glucose regulation.
lobes, is located in front of the windpipe The parathyroid glands are four pea-
(i.e., trachea), just below the voice box sized bodies located behind the thyroid
(i.e., larynx). The gland produces two gland that produce PTH. This hormone
Insulin
structurally related hormones, thyroxine increases calcium levels in the blood, Insulin is produced in the beta cells of the
(T4) and triiodothyronine (T3), that helping to maintain bone quality and Islets of Langerhans. Its primary purpose

160 Alcohol Health & Research World
The Endocrine System

is to lower blood glucose levels; in fact, for maintaining blood sugar levels. Thus, increased cortisol levels repress
insulin is the only blood sugar-lowering Accordingly, disturbances of that balance, CRH release by the hypothalamus
hormone in the body. To this end, insulin such as an insulin deficiency or an inabil- and ACTH release by the pituitary. In
promotes the formation of storage forms ity of the body to respond adequately to addition, ACTH can directly inhibit
of energy (e.g., glycogen, proteins, and insulin, result in serious disorders, such as hypothalamic CRH release.
lipids) and suppresses the breakdown of diabetes mellitus. (For more information Any disturbances in the HPA axis
those stored nutrients. Accordingly, the on diabetes and on alcohol’s effects on can result in serious medical conse-
target organs of insulin are primarily those insulin, glucagon, and the management quences. For example, insufficient
that are specialized for energy storage, such of diabetes, see the article by Emanuele hormone production by the adrenal
as the liver, muscles, and adipose tissue. and colleagues, pp. 211–219.) cortex causes Addison’s disease, which
Specifically, insulin has the following is characterized by muscle weakness,
metabolic effects: dehydration, loss of appetite (i.e.,
Hormone Systems anorexia), nausea, vomiting, diarrhea,
• Promotes glucose uptake into cells fever, abdominal pain, tiredness, and
and its conversion into glycogen, As this article has indicated in describ- malaise. Patients with this disease
stimulates the breakdown of glucose, ing the various endocrine glands and exhibit low levels of plasma cortisol
and inhibits gluconeogenesis their hormones, some hormones are but high levels of ACTH. The increase
controlled directly by the metabolic in ACTH levels represents a vain
• Stimulates the transport of amino pathways that they influence. For attempt by the pituitary to stimulate
acids into cells and protein synthesis example, blood sugar levels directly hormone production in the unrespon-
in muscle cells, thereby lowering the control insulin and glucagon release sive adrenal cortex.
levels of amino acids available for by the pancreas, and calcium levels Equally deleterious is the excessive
gluconeogenesis in the liver in the blood regulate PTH release. glucocorticoid production that results
Conversely, many hormones produced from excess ACTH release (i.e., Cushing’s
• Increases fat synthesis in the liver by target glands are regulated by pituitary syndrome). Those patients experience
and adipose tissue, thereby lower- hormones, which in turn are controlled symptoms such as muscle weakness
ing the levels of glycerol, which by hypothalamic hormones. Examples and wasting, back pain from osteoporo-
also can serve as a starting material of such regulatory hormonal cascades sis, a tendency to bruise easily, redis-
for gluconeogenesis. include the hypothalamic-pituitary- tribution of body fat (i.e., a rounded
adrenal (HPA) axis, the hypothalamic- “moon” face, prominent abdomen,
The release of insulin is controlled pituitary-gonadal (HPG) axis, and the and thin legs), and various psycholog-
by various factors, including blood hypothalamic-pituitary-thyroidal (HPT) ical disturbances. Because of the nega-
glucose levels; other islet hormones axis, which are described briefly in the tive feedback mechanism of the HPA
(e.g., glucagon); and, indirectly, other following sections (see figure 3, p.162). axis, the patient’s cortisol levels are
hormones that alter blood glucose high and the ACTH levels are low.
levels (e.g., GH, glucocorticoids, and Both acute and chronic alcohol
thyroid hormone).
The HPA Axis consumption have been shown to acti-
Activation of the HPA axis, which vate the HPA axis, and some drinkers
regulates various metabolic functions, develop a so-called pseudo-Cushing’s
Glucagon is initiated with the release of CRH syndrome that disappears with absti-
The second blood-sugar–regulating from the hypothalamus. This release nence (Veldman and Meinders 1996;
pancreatic hormone is glucagon, which occurs in response to various stimuli, Emanuele and Emanuele 1997). (For
is produced in the alpha cells of the Islets including almost any type of physical more information on alcohol’s effect on
of Langerhans. Glucagon increases blood or psychological stress; during the nor- the HPA axis and its relation to alcohol
glucose levels; accordingly, its main actions mal sleep-wake cycle; and in response craving, see the article by Gianoulakis,
generally are opposite to those of insulin. to certain neurotransmitters. CRH pp. 202–210.)
For example, glucagon increases glyco- then stimulates the anterior pituitary
gen breakdown and gluconeogenesis in to produce ACTH. (In addition to
the liver as well as the breakdown of lipids CRH, AVP from the hypothalamus
The HPG Axis
and proteins. The release of glucagon is also can stimulate ACTH release). In both men and women, the HPG
regulated by many of the same factors ACTH, in turn, activates adrenal axis is the hormone system that controls
as is insulin’s release, but sometimes with hormone production, primarily the release of sex hormones. In both
the opposite effect. Thus, an increase in of cortisol, which mediates the genders, the system is activated by
blood glucose levels stimulates insulin specific physiological effects of this GnRH, which is released regularly in
release but inhibits glucagon release. hormone system. short bursts from the hypothalamus.
A finely tuned balance between the act- The activity of the HPA axis is regu- GnRH then stimulates the release of
ivities of insulin and glucagon is essential lated by negative feedback mechanisms. FSH and LH from the anterior pituitary.

Vol. 22, No. 3, 1998 161
HPA Axis HPT Axis

+
Stress

Hypothalamus Hypothalamus
+ +
CRH TRH

Anterior Anterior
pituitary pituitary

+ TSH
ACTH

Thyroid
Adrenal gland

+
Kidney

+ T4, T3
Cortisol

Increases
Metabolic metabolism
effects

Female HPG Axis Male HPG Axis

Hypothalamus Hypothalamus
+ +
GnRH GnRH

Anterior Anterior
pituitary pituitary

/+ + +
/+ LH FSH LH FSH

+ +

Ovaries

+ Testes
+

Estrogen Progesterone Testosterone

Figure 3 Schematic representation of the HPA, HPG, and HPT axes. For each system, the hypothalamus secretes releasing
hormones (i.e., CRH, GnRH, and TRH) that act on the pituitary gland. In response to those stimuli, the pituitary gland
releases ACTH, gonadotropins (i.e., LH and FSH), or TSH. ACTH activates the adrenal glands to release cortisol, which
induces metabolic effects. Cortisol also acts back on the hypothalamus and pituitary gland by negative feedback. LH
and FSH in women stimulate the ovaries to produce estrogens and progesterone. Depending on the phase of the men-
strual cycle, those hormones act back on the hypothalamus and pituitary gland in either a stimulatory or inhibitory man-
ner. In men, LH stimulates the testes to release testosterone, which feeds back on the hypothalamus and pituitary.
Finally, TSH stimulates the thyroid gland to produce the thyroid hormones T3 and T4, both of which increase cell
metabolism as well as feed back on the hypothalamus and pituitary.

NOTE: = stimulates; = inhibits; ACTH = adrenocorticotropic hormone; CRH = corticotropin-releasing hormone; FSH = follicle-stimulating hormone;
GnRH = gonadotropin-releasing hormone; HPA = hypothalamic-pituitary-adrenal; HPG = hypothalamic-pituitary-gonadal; HPT = hypothalamic-pituitary-thyroid;
LH = luteinizing hormone; T3 = triiodothyronine; T4 = thyroxine; TRH = thyrotropin-releasing hormone; TSH = thyroid-stimulating hormone.

162 Alcohol Health & Research World
The Endocrine System

Alcohol’s Effects on the
Hypothalamic-Pituitary-Thyroid Axis
One of the essential hormonal systems regulating normal if this change represents a direct effect of long-term
body functioning is the hypothalamic-pituitary-thyroid alcohol consumption or results from co-occurring
(HPT) axis, which controls the metabolism of all cells. As alcohol-related illnesses, because thyroid hormone
with other hormone systems, alcohol consumption under levels are often reduced in patients with acute or chronic
certain conditions can modify the release of hormones non-thyroid–related illnesses, such as sepsis, burns, or
involved in this axis. In healthy nonalcoholics, alcohol major trauma. In addition to the reduced thyroid
consumption does not appear to induce any significant hormone levels, however, the TSH response to TRH
changes in the HPT axis (Emanuele and Emanuele remains blunted in abstinent alcoholics, whereas the pro-
1997). Conversely, some effects of alcohol on the HPT lactin response to TRH has returned to normal levels.
axis have been observed in alcoholics. The effects differ This observation indicates that a factor other than dopa-
depending on the drinking status of the alcoholics mine likely contributes to this effect, although the exact
studied. In alcoholics undergoing withdrawal, baseline mechanisms are unknown.
levels of thyroid hormone (i.e., T3 and T4) in the blood Finally, some intriguing findings have suggested that
differ only minimally from those in nonalcoholics. The abnormal responses of the HPT axis may represent a
ability of hypothalamic thyrotropin-releasing hormone marker for a person’s vulnerability to alcoholism. Thus,
(TRH) to activate the release of thyroid-stimulating some people who are at high risk for developing alcoholism,
hormone (TSH) from the pituitary, however, is impaired such as nonalcoholic sons of alcoholic fathers, tend to
in these alcoholics (Emanuele and Emanuele 1997). exhibit a blunted TSH response to TRH (Emanuele and
This “blunting” effect may result from alcohol’s influence Emanuele 1997). These observations still require further
on the neurotransmitter dopamine. Dopamine produced investigation, however, for researchers to fully understand
in the hypothalamus acts not only as a neurotransmitter their significance.
but also as a hormone in that it inhibits the release of —Susanne Hiller-Sturmhöfel and Andrzej Bartke
both TSH and prolactin from the pituitary. Alcohol
has been shown to increase dopaminergic activity and
thereby may suppress the TSH response to TRH. This References
hypothesis is supported by the fact that prolactin release EMANUELE, N., AND EMANUELE, M.A. The endocrine system: Alcohol
alters critical hormonal balance. Alcohol Health & Research World
in response to TRH also is blunted in alcoholics under- 21(1):53–64, 1997.
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Alcohol’s effects on the HPT axis are even more com- GARBUTT, J.C.; SILVA, S.G.; AND MASON, G.A. Thyrotropin-releasing
hormone (TRH): Clinical neuroendocrine and neurobehavioral findings
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those people, the baseline levels of T3 and sometimes Reviews: Volume 6. Alcohol and Hormones. Totowa, NJ: Humana Press,
T4 are lower than in nonalcoholics. It is unclear, however, 1995. pp. 127–145.

In men, LH stimulates certain substance called inhibin, which luteum. Both hormones participate
cells in the testes (i.e., Leydig cells) prevents FSH release from the in a negative feedback mechanism
to release testosterone. FSH and pituitary. Finally, the Leydig cells through most of the menstrual cycle,
testosterone are key regulators of and, to a lesser extent, the Sertoli suppressing GnRH release from
another set of testicular cells (i.e., cells produce a substance called the hypothalamus and LH release
Sertoli cells), which support and activin, which stimulates FSH from the pituitary. Shortly before
nourish the sperm cells during their secretion and thus has the opposite ovulation, however, a positive feed-
maturation. The HPG axis in men effects of inhibin. back mechanism is activated by
is regulated through a variety of In women, during the menstrual which estradiol actually enhances
factors. For example, testosterone cycle, LH and FSH stimulate the LH release from the pituitary. The
is part of a negative feedback ovarian follicle that contains the resulting surge in LH levels ultimately
mechanism that inhibits GnRH maturing egg to produce estradiol. leads to ovulation, the formation of
release by the hypothalamus and After ovulation has occurred, LH the corpus luteum, and progesterone
LH release by the pituitary. In also promotes production of proges- release. Progesterone exerts a negative
addition, the Sertoli cells secrete a terone and estradiol by the corpus feedback on LH and FSH release,

Vol. 22, No. 3, 1998 163
causing LH levels to decline again. In Summary References
addition to those mechanisms, FSH
CONSTANTI, A.; BARTKE, A.; AND KHARDORI, R.
release from the pituitary is regulated The neuroendocrine system is a Basic Endocrinology for Students of Pharmacy and
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functioning of the HPG axis, resulting hormones are regulated in a fairly W.S.; FRANZ, C.; KAHLE, L.; AND TAYLOR, P.R.
straightforward manner by the end Relation of reported alcohol ingestion to plasma
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in both men and women and in men- products that they influence. Thus, women (Maryland, United States). Cancer Causes
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EMANUELE, N., AND EMANUELE, M.A. The endocrine
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pp. 195–201.)
elaborate feedback mechanisms. In tion and serum estradiol and testosterone levels in
addition, numerous indirect inter- normal postmenopausal women: Relationship to the
The HPT Axis actions exist between the various literature. Alcoholism: Clinical and Experimental
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The hormones that make up the HPT PUROHIT, V. Moderate alcohol consumption and
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REICHMAN, M.E.; JUDD, J.T.; LONGCOPE, C.;
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HPT axis. After reaching the pitu- hormone system may have indirect alcohol consumption on plasma and urinary hor-
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HPT axis, see sidebar, p. 163.) the remaining articles in this issue. ■ Saunders, 1998.

164 Alcohol Health & Research World