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chapter 31
Endocrine Metabolism II: Hypothalamus and Pituitary
TABLE 31-6
Opiomelanocortin Family
Hormone
Site of
Secretion
Peptide
Length
Location
of Gene
Function
Regulation
of Secretion
Adrenocorticotropic
Hormone (ACTH)
(Corticotropin)
Anterior Pituitary
(Corticotroph)
39 aa
2p25
Stimulates steroidogenesis
in all three zones of the
adrenal cortex, thereby
increasing secretion of
cortisol, DHEAS, and
aldosterone.
Stimulated by CRH and
inhibited by cortisol.
/3-Endorphin
Anterior Pituitary
(Corticotroph)
31 aa
2p25
Possible role in stress
analgesia.
Stimulated by CRH and
inhibited by cortisol.
The biological actions of prolactin are initiated by its
membrane receptor, followed by the associated intracellu-
lar signal transduction pathways. These actions are similar
to growth hormone (discussed previously; also see Chapter
30). In humans, the function of PRL may be restricted to
promotion of lactation, but there is some evidence that PRL
suppresses gonadal function in females. There is no con-
sensus regarding a physiological role for PRL in males.
During late pregnancy, the maternal pituitary releases
increasing amounts of PRL in response to rising levels
of estrogen, a stimulator of PRL synthesis. Elevated lev-
els of PRL stimulate milk production in the mammary
gland (Chapter 34). After parturition, PRL promotes milk
secretion via a neuroendocrine reflex that involves sen-
sory receptors in the nipples (Chapter 34). In mammary
tissue, it binds to alveolar cells and stimulates the syn-
thesis of milk-specific proteins (casein, lactalbumin, and
lactoglobulin) by increasing production of their respective
mRNAs. Accordingly, there is a lag of several hours be-
fore this effect of PRL is seen. In the liver, PRL stimulates
the synthesis of its own receptors. PRL receptors occur
in the mammary gland, liver, gonads, uterus, prostate,
adrenals, and kidney.
Disturbances in Prolactin
In women,
hyperprolactinemia
is often associated with
amenorrhea, a condition that resembles the physiological
situation during lactation (lactational amenorrhea). Excess
PRL may inhibit menstrual cyclicity directly by a suppres-
sive effect on the ovary or indirectly by decreasing the
release of GnRH (Chapter 34). In men, hyperprolactine-
mia is not associated with altered testicular function but is
often attended by diminished libido and impotence. This
finding suggests that PRL may serve an important role in
regulating certain behavior patterns.
P rolactin om as
are the
most common hormone-secreting pituitary adenomas and,
in addition to the above-mentioned clinical characteristics,
the patient may exhibit visual field defects. Prolactinoma
may be treated by surgery, radiotherapy, or pharmacother-
apy. This last method consists of using a dopamine D
2
receptor agonist such as bromocriptine or cabergoline to
suppress prolactin secretion.
The Opiomelanocortin Family
All members of this family are derived from a single
prohormone, pro-opiomelanocortin (POMC). The prohor-
mone molecule contains three special peptide sequences:
enkephalin
(opioid),
melanocyte-stimulating hormone
(MSH), and corticotropin (ACTH). These result from post-
translational cleavage of the prohormone but do not share
the same biological actions (Table 31 -
6
). In humans, the
gene encoding POMC is normally expressed in the ade-
nohypophysis, hypothalamus, and brain, as well as in
other sites. It may also be expressed as a result of neo-
plastic transformation, notably in the lung. POMC is a
large glycoprotein that contains three MSH sequences
and one MENK sequence. Several paired basic amino
acid residues exist along the molecule and are sites of
potential cleavage by proteases during posttranslational
processing (Figure 31 -7). In humans, the important prod-
ucts of POMC that are secreted by the adenohypoph-
ysis are ACTH and /3-endorphin, although other prod-
ucts (e.g., y3-MSH, y-LPH) may also be significant (see
later).
After translation POMC is processed by proteases con-
tained in tissue . In the adenohypophyseal corticotrophs
there is no further processing of ACTH and /3-endorphin ,
whereas in the intermediate lobe of other species, ACTH
can be processed to form a-MSH, and y-LPH can be
processed to form /3-MSH. The human hypothalamus
