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

II. Anterior Lobe and Intermediate Lobe
569
TABLE 18-2 Factors Modulating ACTH Release from
the Adenohypophysis
Stimulating
Inhibiting
Hormones CRH Glucocorticoids
Vasopressin
Enkephalin
Peptides
VIP
Neuropeptide Y
Angiotensin II
Cholecystokinin-8
Leptin
Cytokines
TRH, GnRH (in the dog)
Biogenic amines Norepinephrine Dopamine
Serotonin
GABA
Otherwise
Hypoglycemia
Hypoxia
Stress (physical,
emotional)
of desacetyl-, monoacetyl-, and diacetyl- α MSH in secretory
granules. The canine IL contains predominantly the
monoacetyl- α MSH ( Young et al. , 1992 ) .
c . Secretion by the AL
ACTH is released in frequent pulses, as demonstrated in
the pituitary venous effluent of the horse ( Alexander et
al. ,1994; Redekopp et al. , 1986a, 1986b ). By measurements
in peripheral blood ( Kemppainen and Sartin, 1984 ),
the episodic secretion of ACTH in dogs was documented,
with an average of nine peaks per 24-hour period.
Many factors influence the secretion of ACTH by the
AL ( Table 18-2 ). A number of these factors modulate
the release of CRH and AVP, which are considered to be the
predominant stimulating neurohormones in vivo ( Antoni,
1986 ; Keller-Wood and Dallman, 1984 ). The relative contribution
of CRH and AVP to ACTH release varies among
species and circumstances. In dogs ( van Wijk et al. , 1994 )
and pigs ( Minton and Parsons, 1993 ), both exogenously
administered CRH and LVP induce comparably high
plasma ACTH concentrations. In sheep, AVP is the predominant
ACTH-releasing factor. In horses, AVP is the
immediate stimulus for ACTH release, and even ACTH
micropulses appear to be regulated by AVP set point
( Alexander et al. , 1996 ). On the other hand, CRH secretion
and pituitary responsiveness to CRH rise when cortisol
falls, suggesting that in horses a major role for CRH
is to fix the cortisol set point ( Alexander et al. , 1996 ).
In the rat, the stimulation of ACTH release by CRH
and AVP is synergistic, meaning that the response to
CRH AVP is greater than the sum of the reactions to
CRH and AVP separately ( Buckingham, 1987 ).
The basal release of ACTH is regulated by the occupancy
of type I or mineralocorticoid receptors (MR) in the
hippocampus ( Jacobson and Sapolsky, 1991 ). Decreases in
brain MR binding capacity of the dog during aging results
in enhanced basal activity of the hypothalamus-pituitaryadrenal
axis ( Rothuizen et al. , 1993 ). In sheep, basal
ACTH release is inhibited by active immunization against
AVP ( Guillaume et al. , 1992a ) but not by immunization
against AVP ( Guillaume et al. , 1992b ).
Exercise and insulin-induced hypoglycemia stimulate
ACTH release. In the horse, exercise-induced ACTH release
and mild insulin-induced hypoglycemia are accompanied
by increased AVP concentration in pituitary venous blood
without changes in CRH concentrations ( Alexander et al. ,
1991 ). However, when hypoglycemia becomes severe, CRH
is released, which augments the ACTH response ( Alexander
et al. , 1996, 1997 ). In sheep, mild hypoglycemia is accompanied
by increases in AVP and CRH concentrations in portal
blood, but in severe hypoglycemia the AVP secretion is
relatively much higher than the CRH release ( Caraty et al. ,
1990 ). AVP also regulates the ACTH response on hypoglycemia
in the neonatal rat (Muret et al. , 1992) .
Hypotension induced by nitroprusside ( Kemppainen
and Sartin, 1987 ) or by hemorrhage ( Lilly et al. , 1983 )
causes ACTH release in the dog, together with large
increases in plasma AVP derived from the NL ( Raff et al. ,
1989 ). Selective neurohypophysectomy results in greatly
attenuated ACTH and AVP responses to hypotension and
angiotensin II, whereas the ACTH response to CRH injection
remains unchanged. By substitution with adequate
AVP infusion, the ACTH response to hypotension can be
restored ( Raff et al. , 1992 ). In sheep, chronic absence of
ovarian hormones after ovariectomy reduces the ACTH
response to hypotension also, but not to CRH, AVP, or
hypoglycemia ( Pecins-Thompson and Keller-Wood, 1994 ).
In the dog, the release of ACTH is stimulated by
β -adrenergic agonists (isoproterenol), dopaminergic antagonists
(haloperidol), and serotoninergic agonists (quipazine
maleate) . TRH and GnRH stimulate the release of cortisol,
probably by stimulating ACTH release ( Stolp et al. , 1982 ).
In the horse, the α 2-adrenergic agonist clonidine lowers
ACTH secretion primarily by reducing the secretion
of AVP and possibly CRH ( Alexander and Irvine, 2000 ).
Although direct stimulatory effects of catecholamine on
the in vitro release of ACTH from ovine pituitary cells
have been found, central stimulation of predominantly noradrenergic,
but also adrenergic, pathways evokes the highest
ACTH response ( Liu et al. , 1991 ).
Endogenous opiates (metenkephalin, dynorphin, and
β -endorphin) inhibit the release of ACTH in humans
(Besser et al. , 1987). Conflicting results have been reported
on the effect of metenkephalin in the rat, but β -endorphin
and dynorphin may exert tonic inhibition of CRH release
( Plotsky, 1986 ). The metenkephalin agonist DAMME stimulates
the release of ACTH in the dog ( Meij et al. , 1990 ).