Steroid metabolism in the mammalian brain: 5alpha-reduction and aromatization
Steroid metabolism in the mammalian brain: 5alpha-reduction and aromatization
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DOI：
10.1016/s0361-9230(97)00216-5
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发表时间：
1997-01-01
影响因子：
3.8
通讯作者：
Poletti, A
中科院分区：
文献类型：
--
作者：
Celotti, F;NegriCesi, P;Poletti, A
一些类固醇分子，包括雄激素、雌激素、孕激素和皮质类固醇，能够调节大脑的发育和功能。这些化合物在其自身的天然分子结构中并不总是具有活性，但它们通常需要在其靶细胞水平上转化为“活性代谢物”。大脑中转化类固醇的两种主要代谢途径是：5 -还原酶-3 -羟基类固醇脱氢酶和芳香化酶途径。两者都存在于大脑中，可能在激素类固醇的作用机制中发挥特殊作用。在这篇文章中，我们简要地回顾了我们自己和其他实验室在细胞和亚细胞脑分布、发育、调控、克隆和相关酶的分子表征方面取得的一些重要发现。特别是最近鉴定出的两种具有不同结构、生化和分布特征的5 α -还原酶亚型1型和2型，引起了相当大的关注。关于他们大脑分布的少量数据已经被仔细考虑过。最后，我们试图关注类固醇代谢物在大脑中的作用，当它们与基因组和膜受体相互作用时。特别是，一些未发表的关于两种5α -还原酶抑制剂对孕激素诱导麻醉的影响的观察结果，这是一种通过GABA(a)受体介导的现象。(C) 1997爱思唯尔科学有限公司
Several steroid molecules, including androgens, estrogens, progestagens, and corticostereroids, are able to modulate the brain development and functions. These compounds are not always active in their own natural molecular configuration but they often need to be transformed at the level of their target cells into 'active metabolites'. The two major metabolic pathways that transform steroids in the brain are: the 5alpha-reductase-3alpha-hydroxy-steroid dehydrogenase and the aromatase pathways. Both are present in the brain and probably exert specific roles in the mechanism of action of hormonal steroids. In this article we briefly review some important findings achieved in our own and in other laboratories concerning the cellular and subcellular brain distribution, development, regulation, cloning, and molecular characterization of the involved enzymes. In particular, the recent identification of two isoforms of the 5alpha-reductase, the type 1 and type 2, possessing different structural, biochemical, and distribution characteristics has attracted a considerable attention. The few data available on their brain distribution have been carefully considered. Finally, we have tried to focus on the role of the steroid metabolites in the brain, both when they interact with genomic and with membrane receptors. In particular, some unpublished observations on the effects of two 5alpha-reductase inhibitors on progesterone-induced anesthesia, a phenomenon mediated through the GABA(A) receptor, are presented. (C) 1997 Elsevier Science Inc.