GNRH AND THE MENSTRUAL CYCLE

DESCRIPTION (Adapted from the applicant's abstract): The long-range goal of this proposal is to understand the neuroendocrine control of the reproductive cycle, and specifically the role of GnRH in primates. Because of technical difficulties in measuring GnRH release and the long duration of cyclic reproductive events in primates, there is little direct information on the normal GnRH secretory profile during the menstrual cycle - and the available information is fragmentary and controversial. The principal investigator's group has developed a method for measurement of GnRH secretion in the female rhesus monkey by monitoring direct changes in GnRH levels in cerebrospinal fluid (CSF) obtained from the infundibular region of the third ventricle; chronic intraventricular catheterization provides GnRH measurements of long time periods. Five specific aims are proposed to examine GnRH secretory patterns in normal ovulatory menstrual cycles and in pathologic states. Aim 1 will document GnRH secretion throughout individual menstrual cycles and provide for the first time a composite GnRH profile of the normal cycle. Aim 2 will investigate the GnRH secretion at midcycle, at the time when the gonadotropin surge and ovulation occurs, and evaluate the estradiol and progesterone signals required for a proper GnRH/LH surge. Aim 3 will study GnRH secretion at the end of the cycle, during the luteal-follicular transition to consider its role in the reinitiation of follicular growth. Aim 4 will investigate the impact of estrogen negative feedback on GnRH pulsatile release. Aim 5 will study the pathophysiology of GnRH secretion during "stress"-induced hypothalamic amenorrhea, menstrual cycles with inadequate luteal phases, and during treatment cycles for induction of multiple ovulations.