The function and the expression of forebrain GABA(A) receptors change with hormonal state in the adult mouse.

J. Jorge, K. McIntyre, L. Henderson
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引用次数: 37

Abstract

Neurotransmission mediated by gamma-aminobutyric acid type A (GABA(A)) receptors in the mammalian medial preoptic area (mPOA) plays a pivotal role in the expression of hormone-sensitive behaviors. Hand in hand with GABAergic control of reproduction, hormone treatments that activate gonadal steroid signaling pathways in gonadectomized rats are known to regulate the expression of specific GABA(A) receptor subunit mRNAs. While the effects of exogenous hormone treatments have been well documented, little information is available as to how GABA(A) receptor-mediated transmission in the mPOA is altered by endogenous changes in hormonal state in gonadally-intact adult animals or if those changes can be ascribed to hormone-dependent changes in receptor subunit composition. In the present study, we found that both the peak amplitudes of GABA(A) receptor-mediated synaptic currents in the mPOA, as well as the ability of the endogenous neurosteroids to modulate those currents, varied as a function of the estrous cycle. Moreover, we found that the degree of neurosteroid modulation was also significantly different between wild-type and the androgen-insensitive testicular feminization (Tfm) mutant male mice. Semiquantitative RT-PCR analysis performed to assess levels of GABA(A) receptor subunit mRNAs indicated that levels of specific subunits varied over the course of the estrous cycle and between wild-type and Tfm male mice. The variations in GABA(A) receptor expression and function in the mPOA that are associated with differences in gonadal steroid signaling may contribute to the dynamic nature of GABAergic control of neuroendocrine pathways.
成年小鼠前脑GABA(A)受体的功能和表达随激素状态的变化而变化。
哺乳动物内侧视前区(mPOA) γ -氨基丁酸A型(GABA(A))受体介导的神经传递在激素敏感行为的表达中起关键作用。与GABA能控制生殖密切相关的是,在去性腺的大鼠中,激活性腺类固醇信号通路的激素治疗可以调节特异性GABA(A)受体亚基mrna的表达。虽然外源性激素治疗的影响已经有了很好的记录,但关于在性腺完整的成年动物中,GABA(A)受体介导的mPOA传递是如何被内源性激素状态的变化所改变的,或者这些变化是否可以归因于受体亚基组成的激素依赖性变化,目前的信息很少。在本研究中,我们发现在mPOA中GABA(A)受体介导的突触电流的峰值振幅,以及内源性神经类固醇调节这些电流的能力,都随着发情周期的变化而变化。此外,我们发现野生型和雄激素不敏感睾丸雌性化(Tfm)突变雄性小鼠的神经类固醇调节程度也有显著差异。用于评估GABA(A)受体亚基mrna水平的半定量RT-PCR分析表明,特定亚基的水平在发情周期过程中以及野生型和Tfm雄性小鼠之间发生变化。mPOA中GABA(A)受体表达和功能的变化与性腺类固醇信号的差异有关,这可能有助于GABA能控制神经内分泌通路的动态性质。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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