Chapter 11
gland responds, then secondary hyposecretion may be diag-
nosed. By contrast, a failure of the target gland to respond to
the tropic hormone indicates the presence of primary hypo-
secretion. However, this test result sometimes does not dis-
tinguish between the forms of hyposecretion, because in the
absence of tropic hormone for suffi cient duration, the target
gland atrophies. Fortunately, this is often reversible.
The most common means of treating hormone hypose-
cretion is to administer the missing hormone or a synthetic
analog of the hormone. This is normally done either by oral
(pill) or nasal (spray) administration, or by injection.
A hormone can also undergo either
primary hypersecretion
(the gland is secreting too much of the hormone on its own)
secondary hypersecretion
(excessive stimulation of the gland
by its tropic hormone). One of the most common causes of pri-
mary or secondary hypersecretion is the presence of a hormone-
secreting endocrine-cell tumor. These tumors tend to produce
their hormones continually at a high rate, even in the absence
of stimulation (i.e., they are autonomous).
For the diagnosis of primary versus secondary hyperse-
cretion, the concentrations of the hormone and, if relevant,
its tropic hormone are measured. If both concentrations are
elevated, then the hypersecretion is secondary. If the hyper-
secretion is primary, there will be a decreased concentration
of the tropic hormone because of negative feedback from the
high concentration of the hypersecreted hormone.
When an endocrine tumor causes hypersecretion, the
tumor can often be removed surgically or destroyed with radi-
ation if it is confi ned to a small area. In many cases, drugs
that inhibit a hormone’s synthesis can block hypersecretion.
Alternatively, the situation can be treated with drugs that do
not alter the hormone’s secretion, but instead block the hor-
mone’s actions on its target cells.
Hyporesponsiveness and Hyperresponsiveness
In some cases, a component of the endocrine system may not
be functioning normally, even though there is nothing wrong
with hormone secretion. The problem is that the target cells
do not respond normally to the hormone, a condition termed
hyporesponsiveness. An important example of a disease result-
ing from hyporesponsiveness is the most common form of
diabetes mellitus
(called type 2 diabetes mellitus), in which
the target cells of the hormone insulin are hyporesponsive to
this hormone.
One cause of hyporesponsiveness is defi ciency of or abnor-
mal receptors for the hormone. For example, some individuals
who are genetically male have a defect manifested by the absence
of receptors for androgens. Their target cells are unable to bind
androgens, and the result is lack of development of certain male
characteristics, as though the hormones were not being pro-
duced (see Chapter 17 for additional details).
In a second type of hyporesponsiveness, the receptors for
a hormone may be normal, but some event occurring after the
hormone binds to receptors may be defective. For example,
the activated receptor might be unable to stimulate formation
of cyclic AMP or another component of the signaling pathway
for that hormone.
A third cause of hyporesponsiveness applies to hormones
that require metabolic activation by some other tissue after
secretion. There may be a defi
ciency of the enzymes that cata-
lyze the activation. For example, some men secrete testos-
terone (the major circulating androgen) normally and have
normal receptors for androgens. However, these men are
missing the intracellular enzyme that converts testosterone to
dihydrotestosterone, a potent metabolite of testosterone that
binds to androgen receptors and mediates some of the actions
of testosterone on secondary sex characteristics.
In situations characterized by hyporesponsiveness to a
hormone, the plasma concentration of the hormone in ques-
tion is usually elevated, but the response of target cells to
administered hormone is diminished.
Finally, hyperresponsiveness to a hormone can also
occur and cause problems. For example, thyroid hormone
causes an up-regulation of certain receptors for epinephrine;
therefore, hypersecretion of thyroid hormone causes, in turn,
a hyperresponsiveness to epinephrine. One result of this is the
increased heart rate typical of people with elevated levels of
thyroid hormones.
I. The endocrine system is one of the body’s two major
communications systems. It consists of all the glands that
secrete hormones, which are chemical messengers the blood
carries from the endocrine glands to target cells elsewhere in
the body.
Hormone Structures and Synthesis
I. The amine hormones are the iodine-containing thyroid
hormones and the catecholamines secreted by the adrenal
medulla and the hypothalamus.
II. The majority of hormones are peptides, many of which are
synthesized as larger molecules, which are then cleaved into
active fragments.
III. Steroid hormones are produced from cholesterol by the
adrenal cortex and the gonads, and by the placenta during
a. The predominant steroid hormones produced by the
adrenal cortex are the mineralocorticoid aldosterone, the
glucocorticoid cortisol, and two androgens, DHEA and
b. The ovaries produce mainly estradiol and progesterone, and
the testes mainly testosterone.
Hormone Transport in the Blood
I. Peptide hormones and catecholamines circulate dissolved in
the plasma but steroid and thyroid hormones circulate mainly
bound to plasma proteins.
Hormone Metabolism and Excretion
I. The liver and kidneys are the major organs that remove
hormones from the plasma by metabolizing or excreting them.
II. The peptide hormones and catecholamines are rapidly removed
from the blood, whereas the steroid and thyroid hormones are
removed more slowly, in part because they circulate bound to
plasma proteins.
III. After their secretion, some hormones are metabolized to more
active molecules in their target cells or other organs.
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