NEUROPEPTIDE-Y STIMULATES PITUITARY-ADRENAL ACTIVITY IN FETAL AND ADULT SHEEP

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 mu g) 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 mu g) 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. These data show that exogenous administraiton of NPY stimulates pituitary-adrenal activity in fetal and adult sheep. The lack of any direct pituitary effects of NPY suggests that this neuropeptide acts centrally within the brain to exert its effects on the pituitary-adrenal axis.