Pawlak Justyna, Karolczak Magdalena, Krust Andre, Chambon P, Beyer Cordian
Anatomisches Institut, Universität Tübingen, D-72047 Tübingen, Germany.
Glia. 2005 May;50(3):270-5. doi: 10.1002/glia.20162.
Estrogens influence CNS development and a broad spectrum of neural functions. Several lines of evidence also suggest a neuroprotective role for estrogen. Different modes of estrogen action have been described at the cellular level involving classical nuclear estrogen receptor (ER)-dependent and nonclassical membrane ER-mediated rapid signaling. We have previously shown that nonclassical estrogen signaling is implicated in the control of dopamine cell function and protection. Since nonclassical interactions between estrogens and glia may contribute to these effects, our aim was to demonstrate the presence of membrane-associated ERs and their putative coupling to intracellular signaling pathways in astrocytes. Confocal image analysis and fluorescence-activated cell sorting (FACS) studies indicated the attachment of ER-alpha but not ER-beta to the plasma membrane of astrocytes. ERs were located in the cell soma region and glial processes. FACS analysis revealed that only a subpopulation of midbrain astrocytes possesses membrane ER-alpha. In FACS studies on ER-alpha knockout astrocytes, only a few membrane ER-positive cells were detected. The activation of membrane ERs appears to be coupled to the MAP-kinase/Src signaling pathway as shown by Western blotting. In conclusion, our data provide good evidence that nonclassical estrogen action in astrocytes is mediated by membrane ER-alpha. The physiological consequence of this phenomenon is not yet understood, but it might have a pivotal role in estrogen-mediated protective effects on midbrain dopamine neurons.
雌激素影响中枢神经系统的发育以及广泛的神经功能。多项证据还表明雌激素具有神经保护作用。在细胞水平上，已经描述了雌激素作用的不同模式，包括经典的核雌激素受体（ER）依赖性和非经典的膜ER介导的快速信号传导。我们之前已经表明，非经典雌激素信号传导与多巴胺细胞功能的控制和保护有关。由于雌激素与神经胶质细胞之间的非经典相互作用可能导致这些效应，我们的目的是证明星形胶质细胞中存在膜相关ER及其与细胞内信号通路的假定偶联。共聚焦图像分析和荧光激活细胞分选（FACS）研究表明，ER-α而非ER-β附着于星形胶质细胞的质膜。ER位于细胞体区域和神经胶质突起中。FACS分析显示，只有中脑星形胶质细胞的一个亚群具有膜ER-α。在对ER-α基因敲除星形胶质细胞的FACS研究中，仅检测到少数膜ER阳性细胞。如蛋白质免疫印迹所示，膜ER的激活似乎与MAP激酶/ Src信号通路偶联。总之，我们的数据提供了充分的证据，表明星形胶质细胞中的非经典雌激素作用是由膜ER-α介导的。这种现象的生理后果尚不清楚，但它可能在雌激素介导的对中脑多巴胺神经元的保护作用中起关键作用。
