Sex difference in the GABAergic control of gonadotropin release in rats

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GABA is a potent regulator of gonadotropin release in both sexes of rats. Using in vivo microdialysis techniques, we examined 24-hour profiles of GABA release in the medial preoptic area (MPO) where gonadotropin-releasing hormone (GnRH) surge generator resides in female rats. Dialysates were collected at 1-h intervals and sequential blood samples (150μl each) were simultaneously collected under freely moving conditions. The GABA release in the MPO of intact rats showed a marked sexual dimorphism. In male rats, the GABA release is episodic without any daily changes. In female rats, the GABA release showed estrous cycle-dependent changes; it is low at estrus and diestrus 1, increases from the late night of diestrus 2 through the early morning of proestrus, and then rapidly decreases until the afternoon of the day of proestrus followed by the preovulatory luteinizing hormone surge. To further determine the sexual dimorphism of the GABA release, GABA release in the MPO was determined in gonadectomized male and female rats 3 - 5 days after estrogen or cholesterol priming. No sex difference in the serum estradiol concentration was observed in estrogen-primed gonadectomized rats. In ovariectomized estrogen-primed rats, the GABA release was high early in the morning, but clearly declined until the afternoon, when it leveled off. A daily surge-like secretion of luteinizing hormone followed in the afternoon. Conversely, in orchidectomized estrogen-primed rats, the GABA release was high without any daily changes. Ovariectomized or orchiectomized cholesterol-primed rats showed low GABA release and high serum luteinizing hormone concentration without any daily changes. These sexually dimorphic effects of estrogen on the GABA release in the MPO as well as the sexually dimorphic GABA release may contribute to the marked sexual dimorphism of gonadotropin release in rats.