324
Chapter 11
is bound. As we will see next, the degree of protein binding
also infl uences the rate of metabolism and the excretion of the
hormone.
Hormone Metabolism
and Excretion
Once a hormone has acted on a target tissue, the concentration
of the hormone in the blood must be returned to normal. This is
necessary to prevent excessive, possibly harmful effects from the
prolonged exposure of target cells to hormones. A hormone’s
concentration in the plasma depends upon (1) its rate of secre-
tion by the endocrine gland, and (2) its rate of removal from
the blood. Removal, or “clearance,” of the hormone occurs
either by excretion or by metabolic transformation. The liver
and the kidneys are the major organs that excrete or metabolize
hormones.
The liver and kidneys, however, are not the only routes
for eliminating hormones. Sometimes the hormone is metabo-
lized by the cells upon which it acts. Very importantly, in the
case of peptide hormones, endocytosis of hormone-receptor
complexes on plasma membranes enables cells to remove the
hormones rapidly from their surfaces and catabolize them
intracellularly. The receptors are then often recycled to the
plasma membrane.
In addition, enzymes in the blood and tissues rapidly
break down catecholamine and peptide hormones. These
hormones therefore tend to remain in the bloodstream for
only brief periods—minutes to an hour. In contrast, because
protein-bound hormones are protected from excretion or
metabolism by enzymes, removal of the circulating steroid and
thyroid hormones generally takes longer, often several hours.
Thyroid hormone remains in the plasma for days due to very
high binding to plasma proteins.
In some cases, metabolism of a hormone
activates
the
hormone rather than inactivates it. In other words, the secreted
hormone may be relatively inactive until metabolism trans-
forms it. One example is testosterone, which is converted either
to estradiol or dihydrotestosterone in certain of its target cells.
These molecules, rather than testosterone itself, then bind to
receptors inside the target cell and elicit the cell’s response.
Figure 11–8
summarizes the fates of hormones after
their secretion.
Mechanisms of Hormone Action
Hormone Receptors
Before continuing, you may want to review the mechanisms of
ligand:receptor interactions and the signaling pathways acti-
vated by their interactions discussed in Chapter 5. The follow-
ing material is presented in the specifi c context of hormones
and their receptors.
Because hormones are transported in the blood, they
can reach virtually all tissues. Yet the response to a hormone
is highly specifi c, involving only the target cells for that hor-
mone. The ability to respond depends upon the presence of
specifi c receptors for those hormones on or in the target cells.
As emphasized in Chapter 5, the response of a target cell
to a chemical messenger is the fi nal event in a sequence that
begins when the messenger binds to specifi c cell receptors. As
that chapter described, the receptors for peptide hormones
and catecholamines are proteins located in the plasma mem-
branes of the target cells. In contrast, the receptors for ste-
roid hormones and the thyroid hormones are proteins located
mainly
inside
the target cells.
Hormones can infl uence the ability of target cells to
respond by regulating hormone receptors. Again, Chapter 5
described basic concepts of receptor modulation such as up-
regulation and down-regulation. In the context of hormones,
up-regulation
is an increase in the number of a hormone’s
receptors, often resulting from a prolonged exposure to a low
concentration of the hormone. This has the effect of increasing
target-cell responsiveness to the hormone.
Down-regulation
is a decrease in receptor number, often from exposure to high
concentrations of the hormone. This temporarily decreases
target-cell responsiveness to the hormone, thus preventing
overstimulation.
In some cases, hormones can down-regulate or up-
regulate not only their own receptors but the receptors for
other hormones as well. If one hormone induces a loss of a sec-
ond hormone’s receptors, the result will be a reduction of the
second hormone’s effectiveness. On the other hand, a hormone
may induce an increase in the number of receptors for a second
hormone. In this case, the effectiveness of the second hormone
is increased. This latter phenomenon, in some cases, under-
lies the important hormone-hormone interaction known as
permissiveness. In general terms,
permissiveness
means that
hormone A must be present for the full strength of hormone
B’s effect. A low concentration of hormone A is usually all that
is needed for this permissive effect, which may be due to A’s
ability to up-regulate B’s receptors. For example, epinephrine
causes a large release of fatty acids from adipose tissue, but only
Inactivated
by metabolism
Excreted in
urine or feces
Activated
by metabolism
Hormone circulating in blood
Target cells
Bind to receptor and produce
a cellular response
Endocrine cell
Secretes hormone
Figure 11–8
Possible fates and actions of a hormone following its secretion by an
endocrine cell. Not all paths apply to all hormones.
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