section 3i.i
Hypothalamus
733
T A B L E 3 1 - 2
Neurohypophyseal Hormones
Hormone
Structure
9 9
,
Antidiuretic hormone (ADH) (arginine vasopressin)
•— I s .
u
-Tyr
2
-Phe
3
-Gln
4
-Asn
5
-Cys
6
-Pro
7
-Arg
8
-Gly
9
-NH
2
9 9
Oxytocin
Cys
1
-Tyr
2
-Ile
3
-Gln
4
-Asn
5
-Cys
6
-Pro
7
-Leu
8
-Gly
9
-NH
2
principal effect of the hypothalamus on PRL secretion is
inhibitory. A stimulating hormone from the hypothalamus
may be important in tempering the inhibition by dopamine.
Neurohypophyseal Peptides
The magnocellular neurons of the paraventricular and
supraoptic nuclei synthesize antidiuretic hormone (ADH,
vasopressin, or arginine vasopressin) and oxytocin, neu-
ropeptides that are released into the general circulation
in significant amounts (Table 31-2). These neuropeptides
are synthesized in separate cells and transported by ax-
oplasmic flow to nerve endings in the neurohypophysis.
Cholinergic signals to the magnocellular neurons stimu-
late the release of ADH and oxytocin via nerve impulse
propagation along the axon and Ca2+-dependent exocyto-
sis of secretory granules. Release mechanisms for ADH
and oxytocin are under separate control.
ADH is a nonapeptide that contains an intrachain disul-
fide bridge. ADH is synthesized as part of a precursor
glycoprotein (propressophysin), whose gene is located on
chromosome 20. Propressophysin is packaged into secre-
tory granules and transported to the neurohypophysis. Dur-
ing transit, propressophysin is split by proteases in the
granule wall, yielding ADH and a “carrier” polypeptide
called neurophysin II or “nicotine-sensitive neurophysin”
(NSN), whose release is stimulated by nicotine. Upon neu-
ral stimulation, ADH and NSN are released in equimolar
amounts. NSN has no known biological activity. In the
collecting ducts of the kidney, ADH acts by a Gs-protein
coupled cAMP-mediated mechanism to increase the per-
meability of ductal cells to water by mobilizing aquaporin
proteins to the apical membrane which prevents diuresis
(see also Chapter 39). At relatively high concentrations,
ADH is a potent vasoconstrictor. Such concentrations are
attained after massive hemorrhage, when constriction of
blood vessels prevents further blood loss. Major stim-
uli for ADH release are an increase in plasma osmo-
lality, monitored by hypothalamic osmoreceptors, and a
decrease in blood volume, monitored by baroreceptors
in the carotid sinus and in the left atrial wall. Afferent
fibers to the vasomotor center in the hindbrain sense a fall
in blood volume, and diminished noradrenergic signals
from this center to the hypothalamic magnocellular neu-
rons stimulate ADH release. Because norepinephrine in-
hibits ADH release, decrease of this inhibition constitutes
a stimulation.
Oxytocin
is a nonapeptide that differs from ADH at the
residues in positions 3 and
8
. It is synthesized in separate
magnocellular neurons from a gene that codes for pro-
oxyphysin, the precursor of oxytocin and its “carrier” (neu-
rophysin I or estrogen-sensitive neurophysin). Neurons in
the paraventricular and supraoptic nuclei synthesize pro-
oxyphysin, which is packaged and processed during transit
to the neurohypophysis. The principal action of oxytocin
is ejection of milk from the lactating mammary gland
(“milk let-down”), and it also participates in parturition
(Chapter 34). Oxytocin is released by a neuroendocrine
reflex mechanism and stimulates contraction of estrogen-
conditioned smooth muscle cells. The mechanism of ac-
tion of oxytocin does not involve cAMP but may involve
regulation of increased intracellular Ca2+. The oxytocin
receptor belongs to a seven-membrane-spanning receptor
family.
Neuroregulatory Peptides
Neuronal projections from the hypothalamus to other
regions of the brain relay important output informa-
tion that influence blood pressure, appetite, thirst, cir-
cadian rhythm, behavior, nociception (pain perception),
and others factors. Although many of these neurons re-
lease neurotransmitter amines at synapses, some of them
are known to release neurotransmitter peptides. These in-
clude, among others, peptides that closely resemble hor-
mones formed in the gastrointestinal system as well as the
endogenous opiates (Table 31-3).
Brain-Gut Peptides
Gut hormone-like neurotransmitters have been detected
in the brain and are believed to function in a manner that
