Mammalian 3α-hydroxysteroid dehydrogenases

Mammalian 3α-hydroxysteroid dehydrogenases (3α-HSDs) regulate steroid hormone levels. For example, hepatic 3α-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 3α-HSD accts as a molecular switch and controls the amount of 5α- dihydrotestosterone that can hind to the androgen receptor, while in the brain 3α-HSD can regulate the amount of tetrahydrosteroid that can alter GABA(a) receptor function. Molecular cloning indicates that these mammalian 3α-HSDs belong to the aldo-keto reductase superfamily and that they are highly homologous proteins. Using the three-dimensional structure of rat liver 3α- HSD as a template for site-directed mutagenesis, details regarding structure-function relationships, including catalysis and cofactor and steriod hormone recognition have been elucidated. These details may be relevant to all mammalian 3α-HSDs.