The long-term goal of this research is to elucidate the mechanism which causes the regression of the primate corpus luteum at the end of non-fertile menstrual cycles. The specific aim of the current proposal is to determine whether changes in the pattern of secretion of luteinizing hormone during the latter portion of the luteal phase is responsible for regression of the corpus luteum. These studies utilize female rhesus monkeys whose endogenous gonadotropin secretion is terminated by surgically interrupting the communication axis between the hypothalamus and pituitary gland. Menstrual cycles are restored in these animals by the pulsatile infusion of synthetic gonadotropin releasing hormone (GnRH). With this model system, the pattern of circulating LH can be controlled precisely by varying either the frequency of GnRH pulses and/or the amount of GnRH delivered per pulse. We will use this model system to determine i) whether functional luteolysis is the result of the inability of increases in LH pulse amplitude to compensate for reductions in LH pulse frequency during the latter portion of the luteal phase; ii) whether the synergestic actions of estragiol and progesterone in promoting premature luteal regression is the result of modulation of both LH pulse frequency and LH pulse amplitude, and iii) whether endogenously produced estradiol is a luteolysin. In addition to providing definitive information regarding the physiological regulation of the primate corpus luteum in vivo, the information gained from these studies may further our understanding of pathophysiological disturbances of the human menstrual cycle such as the short luteal phase and the inadequate luteal phase. Lastly, it is becoming increasingly apparent that pulsatile GnRH treatment will be used extensively in the treatment of certain types of amenorrhea in humans. The studies presented in this proposal may provide important information regarding the maintenance of the corpus luteum in GnRH-driven menstrual cycles and in doing so, may directly guide clinical endocrinologists in the effective treatment of infertility in humans.