O'Banion M K, Young D A, Bohn M C
Department of Neurology, University of Rochester School of Medicine and Dentistry, NY 14642.
Brain Res Mol Brain Res. 1994 Mar;22(1-4):57-68. doi: 10.1016/0169-328x(94)90032-9.
Glucocorticoids are important in neuronal development, regulation of the hypothalamic-pituitary-adrenal axis, adaptive behavior, and neuronal survival. Glia have receptors for glucocorticoid hormones and thus represent targets for hormone action in the brain. To identify mRNAs that are regulated by corticosterone in primary type 1 rat astrocytes, we have utilized ultra-high resolution giant two-dimensional gel electrophoresis of in vitro translated proteins. Our results reveal 12 in vitro translation products likely representing 10 mRNA species that are regulated by corticosterone. Eleven products are significantly increased and one decreased, most within 3 h of hormone treatment. Inclusion of cycloheximide does not prevent these changes, suggesting that they represent alterations in transcription; however, other mechanisms, such as changes in mRNA stability, cannot be excluded. Two corticosterone-regulated proteins were identified as glucocortin and glutamine synthetase. These two proteins are glucocorticoid-regulated in a variety of cell types, whereas the others appear to be astrocyte-specific. Future identification of these hormone-responsive mRNAs and proteins will help elucidate the molecular basis for glucocorticoid action in the CNS.
糖皮质激素在神经元发育、下丘脑 - 垂体 - 肾上腺轴的调节、适应性行为以及神经元存活方面都很重要。神经胶质细胞具有糖皮质激素的受体,因此是大脑中激素作用的靶点。为了鉴定在原代1型大鼠星形胶质细胞中受皮质酮调节的mRNA,我们利用了体外翻译蛋白质的超高分辨率双向凝胶电泳技术。我们的结果揭示了12种体外翻译产物,可能代表10种受皮质酮调节的mRNA种类。11种产物显著增加,1种减少,大多数在激素处理后3小时内出现变化。加入放线菌酮并不能阻止这些变化,这表明它们代表转录的改变;然而,其他机制,如mRNA稳定性的变化,也不能排除。两种受皮质酮调节的蛋白质被鉴定为糖皮质素和谷氨酰胺合成酶。这两种蛋白质在多种细胞类型中受糖皮质激素调节,而其他蛋白质似乎是星形胶质细胞特异性的。未来对这些激素反应性mRNA和蛋白质的鉴定将有助于阐明糖皮质激素在中枢神经系统中作用的分子基础。