744
chapter 31
Endocrine Metabolism li: Hypothalamus and Pituitary
A n te r io r l y ©
p itu ita ry
1
* N
A d re n a l
c o rte x
C irc a d ia n c u e s
Higher central nervous system centers
S t r e s s
E m o tio n a l d e p r e s s io n
'H y p o th a la m u s !
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C o r t i s o ' y ^ H , , ^ C o r tis o l
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d
F I G U R E 3 1 - 8
Regulation of ACTH secretion in humans.
and antagonists (haloperidol) increase, the synthesis and
release of POMC-derived peptides.
P-Endorphin
is a 31-amino-acid polypeptide released
together with ACTH. When introduced into the third
ventricle of the brain, it produces dramatic behavioral
changes, but when injected systemically, it does not. Thus,
the function of circulating /3-endorphin remains unclear.
The CNS and gastrointestinal effects of the hormone are
probably produced by that secreted locally. Circulating
/
6
-endorphin may act in conjunction with enkephalins
released
by
the
adrenal
medulla
to
produce
stress
analgesia.
Human
N-terminal
fragment
(hNT)
and
7
-
melanocyte stimulating hormone
(y-MSH) are released
with ACTH and /
6
-endorphin. y-MSH, a fragment of hNT.
(Figure 31 -7), may be the putative aldosterone-stimulating
hormone of the pituitary. hNT and y-MSH may also be the
major stimulators of adrenocortical proliferation, whereas
ACTH is the regulator of adrenocortical steroidogenesis.
Glycoprotein Hormones
The glycoprotein hormones may have evolved from a
single ancestral polypeptide (Table 31-7). In the ante-
rior pituitary, the thyrotrophs produce thyrotropin, and the
gonadotrophs produce LH and FSH. Each glycoprotein
hormone is composed of two dissimilar subunits
(a
and
P)
that are glycosylated and noncovalently bound. Synthesis
of
p
subunits is rate limiting. Glycosylation takes place
posttranslationally on the endoplasmic reticulum mem-
branes, at about the time when disulfide bridges form in
each subunit. “Mature” subunits then dimerize and are
packaged in secretory granules.
The
a
subunits of all pituitary glycoprotein hor-
mones are identical but show minor differences from the
a
subunit of hCG. The
p
subunits differ in all and confer
hormonal specificity. The association of
a
and
P
subunits
is required for activity, but the subunits need not be ho-
mologous. Dissociation of the subunits of one hormone,
followed by recombination with subunits of another hor-
mone, results in hybrids that are biologically active and
exhibit the biological activity characteristic of the
p
sub-
unit. For example, the hybrids LH-a/FSH
- / 6
have FSH
activity, while TSH-c*7LH-/6 have LH activity.
The hallmark of glycoprotein hormones is the carbo-
hydrate moiety, particularly in the content of their sialic
acid component, which is proportionate to the half-lives
of the circulating hormones. Their effects are mediated by
intracellular cAMP.
Thyroid-stimulating
hormone
(TSH,
thyrotropin)
stimulates secretion of the thyroid hormones T
4
and T
3
(Chapter 33). It stimulates synthesis of thyroid hormone,
synthesis of thyroglobulin, synthesis of RNA and protein,
uptake and utilization of glucose, and synthesis of phos-
pholipids. TSH also promotes thyroid cell growth (hy-
pertrophy) and vascularization through the gland. All of
these effects are mediated by intracellular cAMP. Release
of TSH is stimulated by TRH and inhibited by circulating
T4. T
4
is converted toT
3
by 5'-deiodinase in the thyrotroph,
and it is T
3
that inhibits the thyrotroph response to TRH.
TRH and T
3
act directly on the thyrotrophs, but TRH elic-
its a prompt release of TSH (within minutes), presumably
via cAMP, whereas T
3
represses the
TSH gene,
and its ef-
fect is evident after several hours. Release of TSH is also
affected by circadian cues and psychogenic signals (see
below). Unlike many subprimate species, the adult human
