The long-term goal of this research project is to characterize the nature, manner, mechanisms and site(s) of action by which central oxytocin (OXY) neurons regulate the release of luteinizing hormone releasing hormone (LHRH) and luteinizing hormone (LH) on the afternoon of proestrus in the cycling female rat. Recent evidence by our laboratory suggests that central OXY neurons may exert a physiologically important stimulatory influence on the release of LHRH and LH occurring just prior to ovulation on the afternoon of proestrus in the cycling female rat (when estradiol levels are physiologically high). The present proposal will test the hypothesis that the stimulatory influence of central OXY neurons on LHRH and LH release is physiologically relevant and depends upon the presence of high levels of plasma estradiol. We will examine the ability of passive immunization against OXY or specific OXY antagonists to affect basal and stimulated levels of plasma LH as well as LHRH content and release occurring on the afternoon of proestrus. We will evaluate the ability of centrally administered OXY to affect LH secretion as well as LHRH content and release on proestrus (when estradiol levels are physiologically high) compared with metestrus (when plasma estradiol is low). The ability of pretreatment with OXY or LHRH antagonists to prevent the OXY-induced effects on plasma LH will be examined in order to demonstrate that the central action of OXY on LH secretion is mediated by LHRH neurons. Finally, we will investigate possible interactions between other physiologically relevant LHRH secretagogues and OXY in regulating LHRH/LH release, and the influence of plasma estradiol levels on their expression, by examining on proestrus and metestrus 1) the ability OXY antagonism to prevent changes in LH caused by the central injection of these secretagogues, and 2) the ability of administration of antagonists or passive immunization against the secretagogues to affect the changes in LH/LHRH release caused by the central injection of OXY. The knowledge gained from these studies should advance our basic understanding concerning the nature, sites, mechanisms and physiological significance of OXY in regulating the preovulatory surge of LH, permit the development of dynamic tests to characterize and diagnose the nature of central causes responsible for the aberrant secretion of LH, and provide insight toward the development of possible novel therapeutic regimens to either alleviate clinical dysfunctions resulting from the abnormal secretion of LH or to cause contraception.
