Environmental stress is recognized as a significant cause of infertility in men and women. However, it is not clear how certain stimuli that activate the pituitary-adrenal axis can interrupt normal reproductive processes in some individuals, but have no effect in others. This proposal describes experiments to investigate the role of vasopressin in stress-induced inhibition of gonadotropin release in intact and gonadectomized male and female macaques. The isolation and purification of corticotropin-releasing hormone (CRH) provided a valuable new tool for investigating the relationship between stress and infertility. Although several studies have supported the hypothesis that CRH may directly inhibit the release of gonadotropin-releasing hormone (GnRH), recent studies from this laboratory in intact primates challenges that hypothesis. Our data show that CRH given at the same dose that blocks electrical activity of the GnRH pulse generator and pituitary LH release in ovariectomized macaques has no effect on LH release in intact rhesus macaques. Evidence from recent human experiments also question the role of CRH in stress-induced inhibition of LH release. The goal of this proposal is to examine the role of vasopressin (VP) in mediating the effects of stresses known to suppress gonadotropin secretion. The first two aims of the present proposal are to determine whether a vasopressin antagonist (VPa) specific to the V1 (pressor) receptors in the brain affects LH release in a psychologically stressful situation in male and female macaques. All of the animals used in these studies will have indwelling catheters which will allow blood sampling and delivery of test substances from a remote site.
The third aim i s to determine if a VPa can block the inhibition of LH release caused by metabolic stressors (fasting and insulin-induced hypoglycemia). In the fourth aim, we will utilize a potent new CRH antagonist to determine whether vasopressin can suppress LH in the absence of the action of CRH. These studies will examine the role of VP in the inhibition of the pituitary-gonadal axis in response to both psychological and metabolic stimuli.
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