Grattan D R, Selmanoff M
Department of Physiology, University of Maryland, School of Medicine, Baltimore 21201-1559.
J Endocrinol. 1994 Oct;143(1):165-74. doi: 10.1677/joe.0.1430165.
The inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) may play an important role in the regulation of LH-releasing hormone secretion. The present study examined the effect of prolactin on GABAergic neuronal activity in microdissected brain regions of the orchidectomized rat, to determine whether inhibition of LH secretion after castration by acute hyperprolactinaemia was associated with prolactin-induced changes in GABAergic neuronal activity. The effects of prolactin were contrasted with the effects of testosterone on hypothalamic GABAergic neurones after orchidectomy. GABA concentrations were measured by high pressure liquid chromatography in eight microdissected brain regions in untreated rats and 60 min after inhibition of the GABA catabolic enzyme GABA transaminase by injection of amino-oxyacetic acid (AOAA). The rate of GABA accumulation in microdissected brain regions following injection of AOAA was taken as an index of GABAergic neuronal activity. Rats were divided into seven experimental groups: intact controls, 2 days after castration, 2 days after castration with prolactin treatment (2.5 mg ovine prolactin injected s.c. every 12 h, starting at the time of castration), 2 days after castration with testosterone replacement (30 mm silicone elastomer implant containing crystalline testosterone), 6 days after castration, 6 days after castration with prolactin treatment, and 6 days after castration with testosterone replacement. Both 2 and 6 days after castration, plasma LH was markedly elevated above levels in intact rats, and AOAA-induced GABA accumulation was significantly decreased in the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis, in the medial preoptic nucleus and in the median eminence. Hyperprolactinaemia significantly reduced LH levels 2 days but not 6 days after castration. GABAergic neuronal activity, however, was not significantly affected by prolactin at either time. Testosterone replacement blocked the postcastration elevation in plasma LH and prevented the castration-induced suppression of GABAergic neuronal activity both 2 and 6 days after castration. There were no castration- or hormone-induced changes in GABAergic neurones observed in the medial or lateral septum, caudate nucleus, cingulate cortex or arcuate nucleus. These results demonstrate that the activity of GABAergic neurones terminating in the rostral hypothalamus and the median eminence is positively regulated by testosterone, and that these steroid-sensitive GABAergic neurones may be important in the negative-feedback control of LH secretion. Inhibition of LH secretion by hyperprolactinaemia, however, may not be mediated by changes in GABAergic neuronal activity.
抑制性氨基酸神经递质γ-氨基丁酸（GABA）可能在促黄体生成素释放激素分泌的调节中发挥重要作用。本研究检测了催乳素对去势大鼠显微切割脑区中GABA能神经元活性的影响，以确定急性高催乳素血症导致去势后促黄体生成素分泌受抑制是否与催乳素诱导的GABA能神经元活性变化有关。将催乳素的作用与睾酮对去势后下丘脑GABA能神经元的作用进行对比。通过高压液相色谱法测量未处理大鼠以及注射氨基氧乙酸（AOAA）抑制GABA分解酶GABA转氨酶60分钟后，八个显微切割脑区中的GABA浓度。注射AOAA后显微切割脑区中GABA的积累速率被用作GABA能神经元活性的指标。大鼠被分为七个实验组：完整对照组、去势后两天、去势后两天并接受催乳素治疗（从去势时开始，每12小时皮下注射2.5毫克羊催乳素）、去势后两天并接受睾酮替代治疗（含结晶睾酮的30毫米硅橡胶植入物）、去势后六天、去势后六天并接受催乳素治疗以及去势后六天并接受睾酮替代治疗。去势后两天和六天，血浆促黄体生成素均显著高于完整大鼠的水平，并且在终板血管器水平的布罗卡斜带、内侧视前核和正中隆起中，AOAA诱导的GABA积累显著减少。高催乳素血症在去势后两天显著降低了促黄体生成素水平，但在六天时未降低。然而，在这两个时间点，催乳素均未对GABA能神经元活性产生显著影响。睾酮替代在去势后两天和六天均阻断了血浆促黄体生成素的术后升高，并防止了去势诱导的GABA能神经元活性抑制。在内侧或外侧隔区、尾状核、扣带回皮质或弓状核中未观察到去势或激素诱导的GABA能神经元变化。这些结果表明，终止于下丘脑前部和正中隆起的GABA能神经元的活性受睾酮正向调节，并且这些对类固醇敏感的GABA能神经元可能在促黄体生成素分泌的负反馈控制中起重要作用。然而，高催乳素血症对促黄体生成素分泌的抑制可能不是由GABA能神经元活性的变化介导的。
