The goal of this proposal is to define the role of a new class of hypothalamic peptides in reproductive endocrinology. These peptides, called atrial natriuretic factors (ANF), exert potent effects on gonadotropin secretion and the studies detailed here will characterize the physiologic consequences of these actions, identify the site of their action and describe the interaction of these peptides with established neuropeptidergic and catecholaminergic systems which regulate the hypothalamo- pituitary-gonadal axis. This information will further our knowledge of the physiological aspects of reproductive function and provide insight into the possible mechanisms responsible for pathologic endocrine states. This proposal deals with the definition of at least one of the hypothalamic factors which can inhibit the endocrinology of reproduction.
Specific aims are to: 1) identify the exact hypothalamic site of action of ANF to inhibit gonadotropin secretion by microinjecting the peptide into specific brain sites and measuring plasma gonadotropins (luteinizing hormone-LH) by radioimmunoassay, 2) identify the class of opiate receptor involved in this action of ANF by using specific opiate antagonists to block its action, 3) investigate the ability of ANF to interact with neurotransmitter systems within the brain which are known to control the secretion of LH-releasing hormone, by using a combination of in vivo and in vitro manipulations which examine the ability of ANF to block catecholamine stimulated LH release or to alter catecholamine synthesis and secretion, 4) correlate in vivo changes in hypothalamic release of ANF with established patterns of LH secretion, and 5) examine the effect of removal of locally produced ANF, by passive immunoneutralization, on LH secretory dynamics. In addition to characterizing the role these peptides play in the hypothalamic control of reporductive endocrinology, these studies will provide valuable insight into other brain actions of ANF and will establish model systems for the further definition of the neural control of reproductive function.
