Grattan D R, Rocca M S, Strauss K I, Sagrillo C A, Selmanoff M, McCarthy M M
Department of Physiology, University of Maryland, School of Medicine, Baltimore 21201-1559, USA.
Brain Res. 1996 Sep 9;733(1):46-55. doi: 10.1016/0006-8993(96)00532-x.
There is considerable evidence that GABAergic neurons play an important role in the regulation of gonadotropin-releasing hormone (GnRH) secretion, and that these neurons may mediate the feedback actions of gonadal steroids on GnRH neurons. The aim of the present study was to investigate whether endogenous changes in ovarian steroid secretion during the estrous cycle influenced GABAergic neuronal activity in the preoptic region of the hypothalamus, and in other steroid-sensitive brain regions. Intact, adult female rats were sacrificed at various times during the days of metestrus or proestrus. GABAergic neuronal activity was estimated by measuring the rate of accumulation of GABA in microdissected brain regions after pharmacological inhibition of GABA degradation. Concentrations of mRNA for both forms of glutamic acid decarboxylase (GAD65 and GAD67) were quantified in microdissected brain regions by a microlysate ribonuclease protection assay. In the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis (DBB(ovlt)), GABAergic neuronal activity was significantly reduced during the afternoon of proestrus compared with the morning of either proestrus or metestrus. In the lateral septal nucleus, GABAergic neuronal activity was significantly increased in the afternoon of proestrus compared with the morning. There were no significant effects of time of day or day of estrous cycle in the medial preoptic nucleus, median eminence, ventromedial nucleus, suprachiasmatic nucleus, medial septal nucleus, hippocampus (CA1 region), or cingulate cortex. In the DBB(ovlt), mRNA levels for both GAD65 and GAD67 were significantly reduced in the afternoon of proestrus compared with the afternoon of metestrus. By contrast, there was no change in GAD65 and GAD67 mRNA levels in the cingulate cortex at any of the times examined. These results demonstrate that GABAergic neuronal activity, and mRNA levels for both GAD65 and GAD67, are reduced in the DBB(ovlt) during the afternoon of proestrus. These results support the hypothesis that decreased GABAergic neuronal activity in this region plays a major permissive role in the generation and maintenance of the estrogen-induced LH surge.
有大量证据表明，γ-氨基丁酸能神经元在促性腺激素释放激素（GnRH）分泌的调节中起重要作用，并且这些神经元可能介导性腺类固醇对GnRH神经元的反馈作用。本研究的目的是调查发情周期中卵巢类固醇分泌的内源性变化是否会影响下丘脑视前区以及其他类固醇敏感脑区的γ-氨基丁酸能神经元活动。在间情期或发情前期的不同时间处死成年雌性大鼠。通过在药理学抑制γ-氨基丁酸降解后测量显微切割脑区中γ-氨基丁酸的积累速率来估计γ-氨基丁酸能神经元活动。通过微裂解物核糖核酸酶保护试验对显微切割脑区中两种形式的谷氨酸脱羧酶（GAD65和GAD67）的mRNA浓度进行定量。在终板血管器水平的布罗卡斜带（DBB(ovlt)），与发情前期或间情期的早晨相比，发情前期下午的γ-氨基丁酸能神经元活动显著降低。在外侧隔核，发情前期下午的γ-氨基丁酸能神经元活动与早晨相比显著增加。在视前内侧核、正中隆起、腹内侧核、视交叉上核、内侧隔核、海马（CA1区）或扣带回皮质，一天中的时间或发情周期的天数没有显著影响。在DBB(ovlt)，与间情期下午相比，发情前期下午GAD65和GAD67的mRNA水平显著降低。相比之下，在任何检查时间，扣带回皮质中GAD65和GAD67的mRNA水平都没有变化。这些结果表明，发情前期下午DBB(ovlt)中的γ-氨基丁酸能神经元活动以及GAD65和GAD67的mRNA水平均降低。这些结果支持了这样一种假说，即该区域γ-氨基丁酸能神经元活动的降低在雌激素诱导的促黄体生成素高峰的产生和维持中起主要的允许作用。
