Rupprecht R, Reul J M, Trapp T, van Steensel B, Wetzel C, Damm K, Zieglgänsberger W, Holsboer F
Max Planck Institute of Psychiatry, Department of Neuroendocrinology, München, Federal Republic of Germany.
Neuron. 1993 Sep;11(3):523-30. doi: 10.1016/0896-6273(93)90156-l.
Several 3 alpha-hydroxysteroids accumulate in the brain after local synthesis or after metabolization of steroids that are provided by the adrenals. The 3 alpha-hydroxy ring A-reduced pregnane steroids allopregnanolone and tetrahydrodeoxycorticosterone are believed not to interact with intracellular receptors, but enhance GABA-mediated chloride currents. The present study shows that these neuroactive steroids can regulate gene expression via the progesterone receptor. The induction of DNA binding and transcriptional activation of the progesterone receptor requires intracellular oxidation of the neuroactive steroids into progesterone receptor active 5 alpha-pregnane steroids. Thus, at physiological concentrations, these neuroactive steroids regulate neuronal function through their effects on both transmitter-gated ion channels and steroid receptor-regulated gene expression.
几种3α-羟基类固醇在局部合成后或肾上腺提供的类固醇代谢后在大脑中积累。3α-羟基A环还原孕烷类固醇别孕烯醇酮和四氢脱氧皮质酮被认为不与细胞内受体相互作用，但可增强GABA介导的氯离子电流。本研究表明，这些神经活性类固醇可通过孕酮受体调节基因表达。孕酮受体的DNA结合诱导和转录激活需要神经活性类固醇在细胞内氧化为孕酮受体活性的5α-孕烷类固醇。因此，在生理浓度下，这些神经活性类固醇通过对递质门控离子通道和类固醇受体调节的基因表达的影响来调节神经元功能。
