Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 18 Pituitary Function
By proteolytic cleavage a variety of N-terminal prolactin
variants have been found. These fragments act on endothelial
cells to suppress vasodilatation and angiogenesis
and promote vascular regression ( Clapp et al. , 2006 ).
It has been suggested that these fragments should be called
“ vasoinhibins. ” In cartilage, the 16kDa N-terminal fragment
is produced from full-length PRL by matrix metalloproteases.
The 16kDa fragment is a potent antiangiogenic
factor ( Macotela et al. , 2006 ).
Prolactin can be phosphorylated at several serine and
threonine residues, which may constitute as much as 80%
of total pituitary PRL in cattle. The degree of glycosylation
may vary from 1% to 60% among species. Finally, dimerization
and polymerization may result in high-molecular
weight forms that in general have reduced biological activity
(Freeman et al. , 2000 ).
c . Secretion
For two reasons, PRL has a unique place among the AL
hormones. First, it is the only hormone that is under tonic
inhibition by the hypothalamus. After transplantation of
the pituitary under the kidney capsule, PRL synthesis is
remarkably enhanced. Second, PRL lacks a specific target
organ that produces factors exerting negative feedback.
The main hypothalamic prolactin-inhibiting factor (PIF)
is dopamine, released primarily from the tuberoinfundibular
dopaminergic neurons located in the arcuate nucleus,
with nerve terminals in the median eminence. Dopamine
released from these neurones is transported to the pituitary
lactotropes via the hypophyseal portal vessels. In addition,
dopamine released from the periventricular hypophyseal
and tuberohypophyseal dopaminergic neurons is released
in the intermediate and neural lobes of the pituitary,
respectively, and reaches the anterior pituitary by means of
short portal vessels. Dopamine activates D2 receptors on
lactotropes to tonically inhibit the release of PRL. In turn,
PRL enters the brain through a receptor-mediated process
in the choroid plexus and stimulates the activity of all three
populations of dopaminergic neurons in the hypothalamus
acting through PRL receptors directly on these dopamine
neurons. In this manner, PRL can regulate its own release
via a short-loop negative feedback ( Andrews, 2005 ).
Apart from this short-loop negative feedback, PRL
secretion from the anterior pituitary gland is controlled by
neuroendocrine factors originating in the hypothalamus
and the posterior pituitary gland, and paracrine factors
originating in the anterior pituitary gland. At the hypothalamic
level, PRL-inhibiting factors are dopamine and
GABA- and PRL-releasing factors are vasoactive intestinal
peptide (VIP) and TRH. At the level of the posterior pituitary
gland, oxytocin and vasopressin, transported to the
lactotropes through the short portal vessels, stimulate PRL
release. Tachykinins, paracrine factors present in the pituitary
gland and brain, can stimulate PRL release through an
indirect (hypothalamus, PRF) or direct stimulatory effect
on lactotropes in the anterior pituitary, or, under some
circumstances, they may inhibit PRL secretion by enhancing
dopamine release from the hypothalamus ( Debeljuk
and Lasaga, 2006 ).
The suckling-, stress-, or estrogen-induced PRL surge
cannot be explained by changes in dopaminergic inhibition
alone. Therefore, the presence of a prolactin-releasing factor
(PRF) has been suggested. Several candidates for the PRF
have been proposed. One of the components of hypothalamic
extracts known to have a stimulatory effect on PRL
release is TRH. This was demonstrated in several mammalian
species, including the pig ( Bevers and Willemse, 1982 ).
However, TRH is probably neither the sole nor the major
physiological PRF. Another strong candidate for PRF is
vasoactive intestinal peptide (VIP) ( Shimatsu et al. , 1985 ).
The rat posterior pituitary was found to contain a potent
PRF ( Hyde et al. , 1987 ). Further analysis demonstrated that
two compounds, oxytocin from the NL and an unidentified
peptide from the IL, could function as PRF. The low potency
of oxytocin made it a less likely candidate for the physiological
regulation of PRL release. The PRF from the IL appeared
to be a small peptide that is present in the posterior pituitary of
many species. Its chemical nature remains to be determined.
Prolactin-releasing peptide (PrRP) was first isolated
from bovine hypothalamus as an orphan G-protein-coupled
receptor ( Hinuma et al. , 1998 ). PrRP was shown to
stimulate PRL secretion in vitro and in vivo ( Matsumoto
et al. , 1999 ). However the effect of PrRP on PRL is less
than that of TRH, and the idea that PrRP was a real hypophysiotropic
PRL-secreting factor has been challenged.
Morphological and physiological studies indicate that
PrRP may play a wide range of roles in neuroendocrinology
other than PRL release, among which the most important
are energy metabolism, metabolic homeostasis, and
stress responses ( Sun et al. , 2005 ).
Like other pituitary hormones, PRL is released in a pulsatile
manner, with fluctuations during different stages of
the reproductive cycle. Apart from an increase around the
time of ovulation ( McNeilly et al. , 1982 ), plasma PRL concentrations
increase during the luteal phase of the sexual
cycle in dogs and cows ( Dieleman et al. , 1986 ) but not in
cats ( Banks et al. , 1983 ). During lactation, very high PRL
concentrations have been found in the sow ( Bevers et al. ,
1978 ) and in the dog ( Concannon et al. , 1978 ). In addition,
distinct increases in PRL concentration have been found in
relation to pregnancy and parturition ( Taverne et al. , 1982 ).
Progesterone induces GH production from the mammary
gland but also modulates the secretion of PRL in
the bitch. In pregnant and overtly pseudopregnant bitches,
the plasma PRL concentration starts to rise about 1 month
after ovulation, which is when the plasma progesterone
concentrations begin to decline. Also in healthy bitches,
most PRL is released during the second half of the luteal
phase. The changes in GH and PRL release during the
luteal phase may promote the physiological proliferation