On the Role of Gonadotropin-Releasing Hormone (GnRH) in the Operation of the GnRH Pulse Generator in the Rhesus Monkey

The pulsatile secretion of luteinizing hormone (LH), occasioned by the pulsatile release of gonadotropin-releasing hormone (GnRH), is closely associated with concurrent increases in multiunit electrical activity in the mediobasal hypothalamus (MUA volleys), the electrophysiological correlates of GnRH pulse generator activity. These volleys represent a highly synchronized increase in firing frequency of individual neurons. The origin of these rhythmic oscillations in unit activity and the mechanisms responsible for their synchronization are unknown. The purpose of the present study was to examine the role, if any, of GnRH in the functioning of the GnRH pulse generator in rhesus monkeys. Ovariectomized animals bearing recording electrodes chronically implanted in the mediobasal hypothalamus and fitted with intracerebroventricular (ICV) cannulae in the lateral ventricle and with indwelling cardiac catheters were studied. LH was measured in venous blood withdrawn from the cardiac catheters every 10 min while hypothalamic electrical activity was monitored continuously. In Experiment 1, following a 3- to 4-hour control period, GnRH was infused ICV at a rate of 300 ng/kg body weight (BW)/h over 4-5 h. In Experiment 2, antide, a long-acting GnRH antagonist, was injected ICV in a dose of 105 mu g/kg BW after a control period of 3-4 h. Additional control experiments were performed in each animal using vehicle alone. Neither GnRH nor antide affected the frequency of MUA volleys and attendant LH pulses despite significant alterations in LH secretion. These results suggest that, in the rhesus monkey, GnRH may not be involved in the operation of the GnRH pulse generator.