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孕酮作为一种神经甾体:在大鼠神经胶质细胞中的合成与作用

Progesterone as a neurosteroid: synthesis and actions in rat glial cells.

作者信息

Jung-Testas I, Do Thi A, Koenig H, Désarnaud F, Shazand K, Schumacher M, Baulieu E E

机构信息

INSERM U 488, Le Kremlin-Bicêtre, France.

出版信息

J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):97-107. doi: 10.1016/s0960-0760(98)00149-6.

DOI:10.1016/s0960-0760(98)00149-6
PMID:10418983
Abstract

The central nervous system (CNS) and the peripheral nervous system (PNS) are targets for steroid hormones where they regulate important neuronal functions. Some steroid hormones are synthesized within the nervous system, either de novo from cholesterol, or by the metabolism of precursors originating from the circulation, and they were termed 'neurosteroids'. The sex steroid progesterone can also be considered as a neurosteroid since its synthesis was demonstrated in rat glial cell cultures of the CNS (oligodendrocytes and astrocytes) and of the PNS (Schwann cells). Both types of glial cells express steroid hormone receptors, ER, GR and PR. As in target tissue, e.g. the uterus, PR is estrogen-inducible in brain glial cell cultures. In the PNS, similar PR-induction could not be seen in pure Schwann cells derived from sciatic nerves. However, a significant PR-induction by estradiol was demonstrated in Schwann cells cocultured with dorsal root ganglia (DRG), and we will present evidence that neuronal signal(s) are required for this estrogen-mediated PR-induction. Progesterone has multiple effects on glial cells, it influences growth, differentiation and increases the expression of myelin-specific proteins in oligodendrocytes, and potentiates the formation of new myelin sheaths by Schwann cells in vivo. Progesterone and progesterone analogues also promotes myelination of DRG-Neurites in tissue culture, strongly suggesting a role for this neurosteroid in myelinating processes in the CNS and in the PNS.

摘要

中枢神经系统(CNS)和外周神经系统(PNS)是类固醇激素的作用靶点,类固醇激素在这些部位调节重要的神经元功能。一些类固醇激素在神经系统内合成,要么由胆固醇从头合成,要么通过循环中前体物质的代谢合成,这些激素被称为“神经甾体”。性类固醇孕酮也可被视为一种神经甾体,因为在中枢神经系统(少突胶质细胞和星形胶质细胞)和外周神经系统(施万细胞)的大鼠神经胶质细胞培养物中已证实其合成。这两种类型的神经胶质细胞都表达类固醇激素受体,即雌激素受体(ER)、糖皮质激素受体(GR)和孕激素受体(PR)。与靶组织(如子宫)一样,在脑胶质细胞培养物中,PR是可被雌激素诱导的。在外周神经系统中,从坐骨神经分离得到的纯施万细胞中未见类似的PR诱导现象。然而,在与背根神经节(DRG)共培养的施万细胞中,雌二醇可显著诱导PR,并且我们将提供证据表明这种雌激素介导的PR诱导需要神经元信号。孕酮对神经胶质细胞有多种作用,它影响少突胶质细胞的生长、分化并增加髓鞘特异性蛋白的表达,还能在体内增强施万细胞形成新的髓鞘。孕酮及其类似物在组织培养中也促进DRG神经突的髓鞘形成,强烈表明这种神经甾体在中枢神经系统和外周神经系统的髓鞘形成过程中发挥作用。

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Progesterone as a neurosteroid: synthesis and actions in rat glial cells.孕酮作为一种神经甾体:在大鼠神经胶质细胞中的合成与作用
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Steroid hormone receptors and steroid action in rat glial cells of the central and peripheral nervous system.类固醇激素受体与类固醇在大鼠中枢和外周神经系统神经胶质细胞中的作用
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Neuronal signals are required for estrogen-mediated induction of progesterone receptor in cultured rat Schwann cells.在培养的大鼠雪旺细胞中,雌激素介导的孕激素受体诱导需要神经元信号。
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Demonstration of steroid hormone receptors and steroid action in primary cultures of rat glial cells.大鼠神经胶质细胞原代培养中类固醇激素受体及类固醇作用的证明
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Progesterone as a neuroactive neurosteroid, with special reference to the effect of progesterone on myelination.孕酮作为一种具有神经活性的神经甾体,特别提及孕酮对髓鞘形成的影响。
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