A STUDY OF THE HYPOTHALAMIC PULSE-GENERATING MECHANISM RESPONSIBLE FOR LH-RELEASE - ELECTRICAL-STIMULATION OF THE MEDIAL BASAL HYPOTHALAMUS IN THE OVARIECTOMIZED GUINEA-PIG

In order to examine the neurophysiological properties of the hypothalamus responsible for the pulsatile release of leuteinizing hormone (LH) the medial basal hypothalamus (MBH) of the ovariectomized adult female guinea pig was stimulated electrically through an implanted electrode and LH release was monitored as an indication of luteinizing hormone-releasing hormone (LHRH) release. Electrical stimulation (ES) consisting of monophasic square wave pulses with 0.5 ms pulse duration was applied for 2 min at 60, 40, 20, or 10 min intervals. Current intensity (80, 200, 500-mu-A) and frequency (8, 50, 100 Hz) were varied to determine the parameters of ES which resulted in an LH pulse with amplitude similar to that of a pulse induced by the endogenous pulse-generating mechanism. Blood samples were collected at 5 or 10 min intervals through an indwelling catheter, and LH was measured by RIA. Results are as follows: (1) spontaneous LH release in animals without ES was pulsatile with a frequency of approximately 32 min; (2) ES induced LH release; if applied during the trough or ascending phase of a spontaneous LH pulse, ES induced in LH pulse 99% of the time, whereas ES induced an LH pulse only 33% of the time if applied during the peak or descending phase of an endogenous LH pulse; (3) the amplitude of LH release induced by ES was related to the number of coulombs applied to the MBH: greater current intensity or greater frequency resulted in an LH pulse with higher amplitude and longer interpulse interval; (4) repeated application of ES at 20 min intervals or longer resulted in an LH response, whereas ES at 10 min intervals did not consistently elicit an LH response. Since the pituitary responded to LHRH challenges at 10 min intervals, the limitation in responding to frequent ES (10 min intervals) occurred at the neural component rather than at the pituitary gland. These results suggest that (i) depolarization of the MBH results in increases in the amplitude of LH release accompanied with increases in interpulse interval of LH release, and (ii) the pulse-generating mechanism responsible for LH release appears to be maximally effective when it is stimulated at intervals between 20 and 40 min, approximating the endogenous rhythmicity of LH release.