Mammalian 3 alpha-hydroxysteroid dehydrogenases

被引：58

作者：

Penning, TM ^{[1
]}

Pawlowski, JE ^{[1
]}

Schlegel, BP ^{[1
]}

Jez, JM ^{[1
]}

Lin, HK ^{[1
]}

Hoog, SS ^{[1
]}

Bennett, MJ ^{[1
]}

Lewis, M ^{[1
]}

机构：

[1] UNIV PENN,SCH MED,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104

来源：

STEROIDS | 1996年 / 61卷 / 09期

关键词：

3 alpha-hydroxysteroid dehydrogenase; aldo-keto reductase; short-chain dehydrogenases/reductases; secosteroids;

D O I：

10.1016/S0039-128X(96)00093-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mammalian 3 alpha-hydroxysteroid dehydrogenases (3 alpha-HSDs) regulate steroid hormone levels. For example, hepatic 3 alpha-HSDs inactivate circulating androgens, progestins, and glucocorticoids. In target tissues they regulate access of steroid hormones to steroid hormone receptors. For example, in the prostate 3 alpha-HSD acts as a molecular switch and controls the amount of 5 alpha-dihydrotestosterone that can bind to the androgen receptor while in the brain 3 alpha-HSD can regulate the amount of tetrahydrosteroids that can alter GABA(a) receptor function. Molecular cloning indicates that these mammalian 3 alpha-HSDs belong to the aldo-keto reductase superfamily and that they are highly homologous proteins. Using the three-dimensional structure of rat liver 3 alpha-HSD as a template for sire-directed mutagenesis, details regarding structure-function relationships, including catalysis and cofactor and steroid hormone recognition have been elucidated. These details may be relevant to all mammalian 3 alpha-HSDs.

引用

页码：508 / 523

页数：16

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