Adler B A, Crowley W R
Endocrinology. 1986 Jan;118(1):91-7. doi: 10.1210/endo-118-1-91.
Recent evidence suggests that gamma-aminobutyric acid (GABA)-containing neurons may inhibit LH release under certain circumstances. The present experiments tested whether GABA agonists block the LH surge induced in ovariectomized rats by estradiol benzoate (EB) plus progesterone (P) treatment and whether these agents affect the concentration and turnover of hypothalamic catecholamines, assessed from the depletion that occurs after synthesis inhibition. Ovariectomized rats received EB, followed 2 days later by P. Simultaneously with P, rats received either saline or one of the GABA agonists, baclofen or muscimol. Other agonist-treated rats received a second injection 4 h later or were additionally treated with the postsynaptic GABA antagonist bicuculline. Additional experiments tested the effects of these agents on LH release in response to exogenous LHRH. The LH surge induced by EB plus P was blocked by administration of either baclofen or muscimol in a dose-dependent manner. Bicuculline did not prevent the effect of baclofen, but partially prevented the effect of muscimol. Neither baclofen nor muscimol significantly affected LH release in rats receiving LHRH. In a second set of studies in EB plus P-treated rats, baclofen and muscimol decreased the steady state concentrations of norepinephrine in the medial preoptic area and medial basal hypothalamus for several hours and markedly decreased the turnover rate of norepinephrine in these areas. The concentrations and turnover of epinephrine were also decreased by these GABA agonists in the medial basal hypothalamus. The drugs had no effect on dopamine levels or turnover in either structure. These results support the hypothesis that a GABAergic system regulates LH release via modulation of noradrenergic and adrenergic systems that control LHRH secretion.
最近的证据表明，含γ-氨基丁酸（GABA）的神经元在某些情况下可能会抑制促黄体生成素（LH）的释放。本实验旨在测试GABA激动剂是否能阻断苯甲酸雌二醇（EB）加孕酮（P）处理诱导的去卵巢大鼠的LH峰，以及这些药物是否会影响下丘脑儿茶酚胺的浓度和周转率，这是通过合成抑制后发生的耗竭来评估的。去卵巢大鼠先接受EB处理，2天后再接受P处理。与P同时，大鼠接受生理盐水或GABA激动剂之一，巴氯芬或蝇蕈醇。其他接受激动剂处理的大鼠在4小时后接受第二次注射，或额外接受突触后GABA拮抗剂荷包牡丹碱处理。额外的实验测试了这些药物对外源性促性腺激素释放激素（LHRH）刺激下LH释放的影响。EB加P诱导的LH峰被巴氯芬或蝇蕈醇以剂量依赖性方式阻断。荷包牡丹碱不能阻止巴氯芬的作用，但部分阻止了蝇蕈醇的作用。巴氯芬和蝇蕈醇均未显著影响接受LHRH的大鼠的LH释放。在另一组针对接受EB加P处理的大鼠的研究中，巴氯芬和蝇蕈醇在数小时内降低了内侧视前区和内侧基底下丘脑去甲肾上腺素的稳态浓度，并显著降低了这些区域去甲肾上腺素的周转率。内侧基底下丘脑的肾上腺素浓度和周转率也被这些GABA激动剂降低。这些药物对两个结构中的多巴胺水平或周转率均无影响。这些结果支持了这样一种假说，即GABA能系统通过调节控制LHRH分泌的去甲肾上腺素能和肾上腺素能系统来调节LH释放。
