The Endocrine System
in the presence of permissive amounts of thyroid hormones
Figure 11–9
). One reason is that thyroid hormones stimu-
late the synthesis of beta-adrenergic receptors for epinephrine
in adipose tissue; thus, the tissue becomes much more sensitive
to epinephrine. It should be noted, however, that receptor up-
regulation does not explain all cases of permissiveness. Often,
the explanation is not known or is due to changes in the signal-
ing pathway that mediates the actions of a given hormone.
Events Elicited by Hormone-Receptor Binding
The events initiated when a hormone binds to its receptor—
that is, the mechanisms by which the hormone elicits a cellular
response—are one or more of the signal transduction pathways
that apply to all chemical messengers, as described in Chapter 5.
In other words, there is nothing unique about the mechanisms
that hormones initiate as compared to those used by neu-
rotransmitters and paracrine/autocrine agents, and so we will
only briefl y review them at this point (see Table 11–2).
Effects of Peptide Hormones and Catecholamines
As stated previously, the receptors for peptide hormones and
the catecholamine hormones are located on the outer surface
of the target cell’s plasma membrane. This location is impor-
tant because these hormones are too large and hydrophilic to
diffuse through the plasma membrane. When activated by hor-
mone binding, the receptors trigger one or more of the signal
transduction pathways described for plasma membrane recep-
tors in Chapter 5. That is, the activated receptors directly infl u-
ence: (1) enzyme activity that is part of the receptor; (2) activity
of cytoplasmic janus kinases associated with the receptor; or
(3) G proteins coupled in the plasma membrane to effector
proteins—ion channels and enzymes—that generate second
messengers such as cAMP and Ca
. The opening or closing of
ion channels changes the electrical potential across the mem-
brane. When a calcium channel is involved, the cytosolic con-
centration of this important ionic second messenger changes.
The changes in enzyme activity are usually very rapid (e.g.,
due to phosphorylation) and produce changes in the activity
of various cellular proteins. In some cases, the signal transduc-
tion pathways also lead to activation or inhibition of particular
genes, causing a change in the synthesis rate of the proteins
coded for by these genes. Thus, peptide hormones and cat-
echolamines may exert both rapid (non-genomic) and delayed
(gene transcription) actions on the same target cell.
Effects of Steroid and Thyroid Hormones
Structurally, the steroid hormones and the thyroid hormones
are all lipophilic, and their receptors, which are intracellular,
constitute part of the steroid hormone receptor superfamily. As
described in Chapter 5, the binding of hormone to one of these
receptors leads to the activation (or in some cases, inhibition)
of the transcription of particular genes, causing a change in the
synthesis rate of the proteins coded for by those genes. The ulti-
mate result of changes in the concentrations of these proteins
is an enhancement or inhibition of particular processes the cell
carries out, or a change in the cell’s rate of protein secretion.
Surprisingly, in addition to having intracellular receptors,
some target cells also have plasma membrane receptors for cer-
tain of the steroid hormones, notably progesterone and estra-
diol. In such cases, the signal transduction pathways initiated
by the plasma membrane receptors elicit rapid, nongenomic
cell responses, whereas the intracellular receptors mediate a
delayed response, requiring new protein synthesis. The physi-
ological signifi cance of the membrane receptors in humans
is still under investigation, but it is clear from animal studies
that these receptors are functional in other vertebrates.
Pharmacological Effects of Hormones
The administration of very large quantities of a hormone for
medical purposes may have effects on an individual that are
not usually seen in a healthy person. These
can also occur in diseases involving the secretion of
excessive amounts of hormones. Pharmacological effects are
of great importance in medicine because hormones are often
used in large doses as therapeutic agents. Perhaps the most
common example is that of very potent synthetic forms of
cortisol, such as prednisone, which is administered to sup-
press allergic and infl
ammatory reactions. In such situations,
a host of unwanted effects may be observed (as described in
Additional Clinical Examples at the end of Section D).
Little or no
fatty acids
Small amount
of fatty acids
Large amount
of fatty acids
nt of f
Figure 11–9
The ability of thyroid hormone to “permit” epinephrine-induced
release of fatty acids from adipose tissue cells. Thyroid hormone
exerts this effect by causing an increased number of epinephrine
receptors on the cell. Thyroid hormone by itself stimulates only a
small amount of fatty acid release.
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