Martínez de la Escalera G, Choi A L, Weiner R I
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California School of Medicine, San Francisco.
Neuroendocrinology. 1994 May;59(5):420-5. doi: 10.1159/000126687.
The mouse GT1 gonadotropin-releasing hormone (GnRH) neuronal cell lines exhibit highly differentiated properties of GnRH neurons. This report investigates the direct effect of gamma-aminobutyric acid (GABA) and subtype selective GABA agonists on GnRH secretion by GT1 cells in perifusion. Treatment of GT1-1 cells with GABA (10 microM) for 100 min resulted in a biphasic release of GnRH. A rapid and sharp stimulation of GnRH secretion was followed by a sustained inhibition of GnRH secretion. During the inhibitory phase, pulses of GnRH assessed by 'cluster analysis' were totally suppressed. The GABAA receptor agonist muscimol (10 microM) stimulated a rapid but transient release of GnRH. On the other hand, treatment of GT1-1 cells with the GABAB receptor agonist baclofen (10 microM) resulted in the prolonged inhibition of GnRH secretion which returned to normal after the treatment stopped. These results demonstrate a direct biphasic effect of GABA upon GnRH release. The initial stimulation appears to be mediated via GABAA receptors, while the sustained inhibition of GnRH secretion appears to involve the activation of GABAB receptors.
小鼠GT1促性腺激素释放激素(GnRH)神经元细胞系表现出GnRH神经元高度分化的特性。本报告研究了γ-氨基丁酸(GABA)及其亚型选择性GABA激动剂对灌流培养的GT1细胞分泌GnRH的直接作用。用GABA(10微摩尔)处理GT1-1细胞100分钟导致GnRH呈双相释放。GnRH分泌先出现快速且急剧的刺激,随后是GnRH分泌的持续抑制。在抑制期,通过“聚类分析”评估的GnRH脉冲完全被抑制。GABAA受体激动剂蝇蕈醇(10微摩尔)刺激GnRH快速但短暂地释放。另一方面,用GABAB受体激动剂巴氯芬(10微摩尔)处理GT1-1细胞导致GnRH分泌的长期抑制,在处理停止后恢复正常。这些结果表明GABA对GnRH释放有直接的双相作用。最初的刺激似乎是通过GABAA受体介导的,而GnRH分泌的持续抑制似乎涉及GABAB受体的激活。