ACUTE ESTRADIOL MODULATION OF ELECTRICAL-ACTIVITY OF THE LHRH PULSE-GENERATOR IN THE OVARIECTOMIZED RAT - RESTORATION BY NALOXONE

Whether estrogen has the brain as a site of its negative feedback action was investigated by checking the acute effect of estradiol-17 beta (E(2)) on the electrical activity of the luteinizing hormone-releasing hormone (LHRH) pulse generator in ovariectomized rats fitted with chronically implanted electrode arrays in the medial basal hypothalamus. Before subcutaneous E(2) implantation, the hypothalamic multiunit activity (MUA) exhibited, at an average frequency of 2.43/h, characteristic increases (volleys), each of which was associated with the initiation of an LH pulse. Within 2 h after E(2) implantation, the frequency of MUA volleys was reduced significantly, probably associated with decreases in the frequency of LH pulses. The decrease in the amplitude of LH pulses occurred later than 2 h, but this effect was considered not to be mediated by the brain since the duration of MUA volleys was not changed. Since the mean serum LH concentration started to decrease within 2 h after E(2) implantation, it was concluded that the acute inhibitory E(2) effect on LH release is mediated by the brain. On the day after E(2) implantation, intravenous infusion of naloxone (2 mg/kg/h) promptly elicited intermittent MUA volleys each of which was associated with an LH pulse. This suggests that operation of the LHRH pulse generator in the ovariectomized condition is restrained by the action of E(2) With the mediation of endogenous opioid peptide neurons.