Sex difference in the GABAergic control of gonadotropin release in rats

GABA是两性大鼠促性腺激素释放的有效调节剂。利用体内微透析技术，我们检测了雌性大鼠内侧视前区（MPO）的24小时GABA释放谱，其中MPO是促性腺激素释放激素（GnRH）的峰值发生器。每隔1 h采集透析液，并在自由移动的条件下同时采集顺序血样（每次150μl）。完整大鼠MPO中GABA的释放表现出明显的性别二态性。在雄性大鼠中，GABA的释放是间歇性的，没有任何日常变化。在雌性大鼠中，GABA的释放表现出依赖于发情周期的变化；在发情期和退情期1时较低，从退情期2的深夜到发情前期的清晨增加，然后迅速减少，直到退情当天的下午，排卵前促黄体激素激增。为了进一步确定GABA释放的性别二态性，在雌激素或胆固醇启动后3 - 5天，测定了性腺去角质的雄性和雌性大鼠MPO中GABA的释放。雌激素诱导的性腺去角质大鼠血清雌二醇浓度无性别差异。在卵巢切除的雌激素刺激大鼠中，GABA的释放在清晨很高，但明显下降，直到下午才趋于平稳。每天下午，黄体生成素的分泌激增。相反，在兰花切除的雌激素刺激大鼠中，GABA的释放量很高，没有任何日常变化。去卵巢或去睾丸胆固醇引发的大鼠GABA释放低，血清黄体生成素浓度高，无任何日常变化。雌性激素对大鼠MPO中GABA释放的性别二态性影响以及GABA的性别二态性释放可能是促性腺激素释放显着的性别二态性的原因。

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.