title: Mammalian 3 alpha-hydroxysteroid dehydrogenases.
abstract: 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 GABAa 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 site-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.
authors.affiliation: Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104-6084, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Penning
authors.forename: J E
authors.initials: JE
authors.lastname: Pawlowski
authors.forename: B P
authors.initials: BP
authors.lastname: Schlegel
authors.forename: J M
authors.initials: JM
authors.lastname: Jez
authors.forename: H K
authors.initials: HK
authors.lastname: Lin
authors.forename: S S
authors.initials: SS
authors.lastname: Hoog
authors.forename: M J
authors.initials: MJ
authors.lastname: Bennett
authors.forename: M
authors.initials: M
authors.lastname: Lewis
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D005544:Forecasting; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011467:Prostate / Q000201:enzymology; D011487:Protein Conformation; D011817:Rabbits; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013256:Steroids / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D013256:Steroids; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)