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雌激素对大鼠视前区γ-氨基丁酸传递的调节作用

Estrogen regulation of GABA transmission in rat preoptic area.

作者信息

Herbison A E

机构信息

Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge, UK.

出版信息

Brain Res Bull. 1997;44(4):321-6. doi: 10.1016/s0361-9230(97)00210-4.

DOI:10.1016/s0361-9230(97)00210-4
PMID:9370195
Abstract

The medial preoptic area represents a brain region where gonadal steroids act upon classical nuclear receptors to alter brain function. Of all the neuronal phenotypes shown to express estrogen receptors in the preoptic area, GABA neurones are the most abundant and known to be located in several nuclei of the medial preoptic area. Investigators utilising techniques capable of assessing endogenous GABA levels have shown that estrogen increases both basal and stimulated extracellular GABA concentrations within the preoptic area. Experiments have also shown that estrogen is able to modulate the actions of noradrenaline upon preoptic GABA neurones. The precise nature of estrogen's stimulatory influence on preoptic GABA concentrations is not understood fully but appears to involve changes in both the release and reuptake of GABA. As estrogen does not influence glutamic acid decarboxylase activity or gene expression in the preoptic area, the subcellular mechanism(s) through which estrogen enhances GABA release remain unknown. Recent investigations indicate that estrogen upregulates transcription of the GAT-1 GABA transporter gene in the preoptic area, and that this may contribute the stimulatory effect of estrogen on extracellular GABA concentrations. Further studies have identified effects of estrogen on GABA(A) receptor expression and ligand binding and, together with the above observations, demonstrate a coordinated and multifaceted upregulation of the preoptic GABA network by estrogen. It is suggested that estrogen acts directly upon GABA neurones expressing estrogen receptors to alter the dynamics of inhibitory transmission within specific neuronal networks of the preoptic area. This is likely to be of functional significance to the "feedback" influence of estrogen on the neural regulation of reproduction.

摘要

内侧视前区是一个脑区,性腺类固醇作用于经典核受体以改变脑功能。在视前区所有已显示表达雌激素受体的神经元表型中,γ-氨基丁酸(GABA)神经元最为丰富,且已知位于内侧视前区的几个核团中。利用能够评估内源性GABA水平的技术的研究人员表明,雌激素可增加视前区内基础和刺激后的细胞外GABA浓度。实验还表明,雌激素能够调节去甲肾上腺素对视前区GABA神经元的作用。雌激素对视前区GABA浓度的刺激影响的确切性质尚未完全了解,但似乎涉及GABA释放和再摄取的变化。由于雌激素不影响视前区谷氨酸脱羧酶的活性或基因表达,雌激素增强GABA释放的亚细胞机制仍然未知。最近的研究表明,雌激素上调视前区GAT-1 GABA转运体基因的转录,这可能有助于雌激素对细胞外GABA浓度的刺激作用。进一步的研究已经确定了雌激素对GABA(A)受体表达和配体结合的影响,并且与上述观察结果一起,证明了雌激素对视前区GABA网络的协同和多方面的上调。有人提出雌激素直接作用于表达雌激素受体的GABA神经元,以改变视前区特定神经元网络内抑制性传递的动态。这可能对雌激素对生殖神经调节的“反馈”影响具有功能意义。

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