Herbison A E, Fénelon V S
Laboratory of Neuroendocrinology, Brabraham Institute, Cambridge, UK.
J Neurosci. 1995 Mar;15(3 Pt 2):2328-37. doi: 10.1523/JNEUROSCI.15-03-02328.1995.
This study has examined whether circulating estrogens are involved in regulating gamma-aminobutyric acid (GABA)A receptor mRNA expression in regions of the female rat brain known to contain estrogen receptors (ERs). In situ hybridization experiments using 35S-labeled oligonucleotides specific for alpha 2, beta 3, and gamma 1 subunit mRNAs of the GABAA receptor demonstrated that all three mRNAs were abundant in only the medial preoptic nucleus (MPN), where they were expressed by the vast majority of cells, and specific regions of the bed nucleus of the stria terminalis including the principle encapsulated nucleus (PrN-BNST) and bed nucleus of the anterior commissure (BNAC). Estrogen treatment of ovariectomized rats for 7 d resulted in significant 30-60% increases in alpha 2 and gamma 1, but not beta 3, subunit mRNA expression in the MPN and PrN-BNST. Estrogen treatment for 24 hr resulted in levels of mRNA expression intermediate between those of controls and animals treated with estrogen for 7 d. No changes in subunit mRNA expression were detected for any subunit in the BNAC or cingulate cortex. Double-labeling immunocytochemistry experiments using antibodies directed against the alpha 2 subunit of the GABAA receptor and the ER, revealed that 67 +/- 3% of alpha 2 subunit-immunoreactive cells in the MPN also contained ER immunoreactivity. Cells expressing alpha 2 subunits in the PrN-BNST were also found to possess ERs while those in the BNAC and cingulate cortex did not. These findings suggest the possibility that ER-containing cells in the MPN and PrN-BNST express an alpha 2 beta 3 gamma 1 isoform of the GABAA receptor that has its alpha 2 and gamma 1 subunits regulated by circulating estrogen concentrations. Together, our observations indicate that estrogen may regulate GABAA receptor mRNA expression at a transcriptional level and that this is only likely to occur within regions of the rat brain possessing ERs.
本研究检测了循环雌激素是否参与调节雌性大鼠脑中已知含有雌激素受体（ERs）区域的γ-氨基丁酸（GABA）A受体mRNA表达。使用针对GABAA受体α2、β3和γ1亚基mRNA的35S标记寡核苷酸进行的原位杂交实验表明，所有这三种mRNA仅在内侧视前核（MPN）中大量存在，绝大多数细胞在此处表达这些mRNA，终纹床核的特定区域包括主包囊核（PrN-BNST）和前连合床核（BNAC）也有表达。对去卵巢大鼠进行7天的雌激素处理，导致MPN和PrN-BNST中α2和γ1亚基mRNA表达显著增加30%-60%，但β3亚基mRNA表达未增加。雌激素处理24小时导致mRNA表达水平介于对照组和接受7天雌激素处理的动物之间。在BNAC或扣带回皮质中，未检测到任何亚基的亚基mRNA表达变化。使用针对GABAA受体α2亚基和ER的抗体进行的双标记免疫细胞化学实验显示，MPN中67±3%的α2亚基免疫反应性细胞也含有ER免疫反应性。在PrN-BNST中表达α2亚基的细胞也被发现含有ERs，而在BNAC和扣带回皮质中的细胞则没有。这些发现提示了一种可能性，即MPN和PrN-BNST中含有ER的细胞表达GABAA受体的α2β3γ1异构体，其α2和γ1亚基受循环雌激素浓度调节。总之，我们的观察结果表明，雌激素可能在转录水平上调节GABAA受体mRNA表达，并且这仅可能发生在大鼠脑中具有ERs的区域内。
