ACUTE ACTION OF ESTROGEN ON MEDIAL PREOPTIC GAMMA-AMINOBUTYRIC-ACID NEURONS - CORRELATION WITH ESTROGEN NEGATIVE FEEDBACK ON LUTEINIZING-HORMONE SECRETION

The acute effects of oestrogen on the medial preoptic area (MPOA) gamma-aminobutyric acid (GABA) system were examined by delivering an intravenous bolus of 17-beta-oestradiol (5-mu-g/100 g body wt) to conscious ovariectomized rats implanted with microdialysis probes. Fifteen-min blood samples were taken to determine the time-course of negative feedback effects of oestrogen on luteinizing hormone (LH) secretion. Two h after administration of 17-beta-oestradiol, GABA release from the MPOA was significantly elevated compared with vehicle-treated controls (P < 0.05). The rise in GABA levels continued until the end of the experiment, 4 h after 17-beta-oestradiol, at which time it was over 50% higher than controls (P < 0.01). The pulsatile pattern of LH secretion was significantly depressed 2 and 3 h after administration of 17-beta-oestradiol compared with controls (P < 0.05). To determine the effects of the 17-beta-oestradiol treatment on pituitary responsiveness to LH-releasing hormone (LHRH), a further group of rats were given exogenous LHRH (50 ng/100 g body wt, intravenously) before and 3 h after vehicle or 17-beta-oestradiol treatment and blood samples taken to determine the effect on LH secretion. The maximal LH response to LHRH in 17-beta-oestradiol-treated rats was approximately 50% that of control-treated values. This study demonstrates the acute and potent action of 17-beta-oestradiol on GABA release in the MPOA and lends support to a genomic site of action for oestrogen in modulating neural elements regulating GABA release from the MPOA. These results, showing a parallel decrease in LH secretion with increased GABA levels in the MPOA, suggest a role for GABA elements within the MPOA as a site of oestrogen negative feedback on LH secretion.