Neuropeptide‐Y Stimulates Pituitary‐Adrenal Activity in Fetal and Adult Sheep

Abstract

Corticotrophin-releasing factor (CRF) and arginine vasopressin (AVP) are the primary neuropeptides regulating the secretion of ACTH from the anterior pituitary gland during fetal and adult life. However, a number of other neuropeptides including neuropeptide-Y (NPY) appear to modulate the activity of this system. The potential role of NPY in the regulation of pituitary-adrenal function was examined in fetal and adult sheep. Administration of NPY (6.5 micrograms) as a bolus injection into the third cerebral ventricle of adult ewes elicited a significant (P < 0.05) increase in plasma concentrations of ACTH. In fetal sheep at day 125 gestation (term = 145 days) a five-fold higher dose (30 micrograms) of NPY injected into the lateral cerebral ventricles also caused a significant increase in plasma concentrations of ACTH. The potential of NPY to influence ACTH secretion directly from the pituitary gland was investigated using primary cultures of fetal (day 130 gestation) and adult pituitary cells. CRF (10(-10)-10(-7) M) caused a significant (P < 0.01) dose-related increase in ACTH secretion from both fetal and adult pituitary cells. Furthermore, the secretion of ACTH from adult cells was significantly greater (P < 0.05) than that from fetal cells. NPY (10(-10)-10(-7) M) had no effect on basal or CRF-stimulated ACTH secretion from fetal or adult pituitary cells. Pre-incubation of pituitary cells with cortisol (10(-9) and 10(-7) M) for three days significantly inhibited CRF-stimulated ACTH secretion but had no effect on basal ACTH release. The simultaneous addition of NPY did not alter the ability of cortisol to inhibit CRF-stimulated ACTH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactions between the neuropeptide Y system and the hypothalamic-pituitary-adrenal axis

“…However, the effect of NPY at the level of the pituitary gland seems to be weaker than that in the hypothalamus and is speciesdependent (11,15). In the study by Brooks et al (11), NPY did not affect ACTH release in the cultures of pituitary cells from adult and fetal sheep, whereas ACTH release increased in the sheep pituitary in situ. These findings suggest that ACTH secretion is indirectly enhanced as a result of NPY acting at one or more suprahypophysial brain sites.…”

“…These findings suggest that ACTH secretion is indirectly enhanced as a result of NPY acting at one or more suprahypophysial brain sites. Moreover, NPY did not alter the CRF-stimulated release of ACTH in sheep, and it did not modulate the ability of cortisol to inhibit CRF induced ACTH secretion (11). In contrast, NPY stimulates HPA axis activity in the dog pituitary, because NPY injected in subthreshold doses into the third ventricle potentiates the effect of CRF on ACTH release (15).…”

“…In vitro (7) and in vivo (8,9) studies have revealed that NPY stimulates CRF release and increases CRF gene expression (10). Consequently, the level of pro-opiomelanocortin mRNA increases (10), as does the release of ACTH (9)(10)(11), cortisol (12), and corticosterone (13,14). NPY influences the HPA axis in a dose-dependent manner (10,15).…”

“…NPY influences the HPA axis in a dose-dependent manner (10,15). In vivo, the HPA axis is stimulated by NPY given by different routes: into the lateral ventricle (10,13), the third ventricle (11,15), the cistern (8), intravenously (10), or directly into the PVN (9,14). The greatest CRF release was induced by picomolar doses of NPY injected into the PVN, which proves that the PVN has an important role in the activation of the HPA axis by NPY.…”

Chronic central neuropeptide Y infusion in normal rats: status of the hypothalamo-pituitary-adrenal axis, and vagal mediation of hyperinsulinaemia

“…Such NPY-induced changes include increases in corticotropin-releasing factor (CRF) mRNA levels and immunoreactivity in the PVN [29,30], and increases in plasma adrenocorticotropic hormone (ACTH) and corticosterone concentrations [3]. In vitro, NPY stimulates CRF secretion from hypothalamic fragments [3], and it may also increase the sensitivity of cultured pituitary cells to CRF-induced secretion of ACTH [3], although this has not been a unanimous finding [31,32]. There is some evidence that endogenous NPY may influence the activity of the HPA axis in vivo, since NPYergic nerve terminals have been shown to make contact with CRF-synthesising perikaryon of the PVN [3], and since i. c. v. infusion of anti-NPY serum eliminated the stress-induced increase in plasma ACTH concentrations in dogs [3].…”