Melcangi R C, Magnaghi V, Cavarretta I, Riva M A, Martini L
Department of Endocrinology, University of Milan, Italy.
J Neuroendocrinol. 1997 Oct;9(10):729-33. doi: 10.1046/j.1365-2826.1997.00621.x.
The paper describes the effects of corticosterone and deoxycorticosterone (DOC), used in their native or in their 5 alpha-reduced molecular forms (dihydrocorticosterone, DHC; dihydrodeoxycorticosterone, DHDOC; and tetrahydrodeoxycorticosterone, THDOC) on the gene expression of the myelin basic protein (MBP) and of the glial fibrillary acidic protein (GFAP) in pure cultures, respectively, of oligodendrocytes and type 1 astrocytes obtained from the neonatal rat brain. Among the different steroids tested (corticosterone, DHC, DOC, DHDOC and THDOC), only DHDOC was effective on the gene expression of MBP in the oligodendrocyte cultures; the mRNA levels of this typical oligodendrocyte marker were decreased following exposure to this steroid for 24 h. In the case of the astrocytic marker GFAP, its gene expression was increased by the exposure to corticosterone for 6 and 24 h, while DHC was ineffective; the mineralocorticoid DOC was also ineffective, while its 5 alpha-reduced derivative, DHDOC, strongly inhibited GFAP gene expression, starting at 6 h after beginning of the treatment. In conclusion, the present data show that: (1) adrenal steroids possessing gluco- and mineralocorticoid activities may influence the gene expression of the astrocytic marker GFAP; (2) the 5 alpha-reduced metabolite of DOC, DHDOC is able to influence the gene expression not only of GFAP but also that of MBP, which are, respectively, typical markers of the astrocytes and the oligodendrocytes; (3) the metabolic conversion of hormonal steroids into their 5 alpha-reduced metabolites, which also occurs in the glia, could be implicated in the biochemical control of oligodendrocyte and astrocyte functions.
该论文描述了皮质酮和脱氧皮质酮（DOC），以其天然形式或5α-还原分子形式（二氢皮质酮，DHC；二氢脱氧皮质酮，DHDOC；和四氢脱氧皮质酮，THDOC）分别对从新生大鼠脑获得的少突胶质细胞和1型星形胶质细胞纯培养物中髓鞘碱性蛋白（MBP）和胶质纤维酸性蛋白（GFAP）基因表达的影响。在所测试的不同类固醇（皮质酮、DHC、DOC、DHDOC和THDOC）中，只有DHDOC对少突胶质细胞培养物中MBP的基因表达有效；暴露于该类固醇24小时后，这种典型的少突胶质细胞标志物的mRNA水平降低。对于星形胶质细胞标志物GFAP，暴露于皮质酮6小时和24小时后其基因表达增加，而DHC无效；盐皮质激素DOC也无效，而其5α-还原衍生物DHDOC在治疗开始后6小时开始强烈抑制GFAP基因表达。总之，目前的数据表明：（1）具有糖皮质激素和盐皮质激素活性的肾上腺类固醇可能影响星形胶质细胞标志物GFAP的基因表达；（2）DOC的5α-还原代谢产物DHDOC不仅能够影响GFAP的基因表达，还能影响MBP的基因表达，它们分别是星形胶质细胞和少突胶质细胞的典型标志物；（3）激素类固醇向其5α-还原代谢产物的代谢转化，这也发生在神经胶质细胞中，可能与少突胶质细胞和星形胶质细胞功能的生化控制有关。
