title: Genetic analysis of 11 beta-hydroxysteroid dehydrogenase.
abstract: 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) catalyzes the interconversion of cortisol and cortisone. This activity is postulated to protect the Type I (mineralocorticoid) receptor from excessive concentrations of cortisol, allowing aldosterone to function as a mineralocorticoid. An enzyme with 11 beta-OHSD activity was isolated from rat liver and the corresponding rat and human cDNA and genomic clones isolated. This enzyme is a member of the short-chain dehydrogenase family. Using site-directed mutagenesis, it was demonstrated that the amino terminus and two highly conserved residues, Tyr-179 and Lys-183, are required for enzymatic function. Examination of patients with apparent mineralocorticoid excess, a syndrome of juvenile hypertension thought to represent 11 beta-OHSD deficiency, did not reveal any mutations in the HSD11 gene. This disorder may involve an additional enzyme with 11 beta-OHSD activity or possibly another cortisol metabolizing enzyme.
authors.affiliation: Division of Pediatric Endocrinology, Cornell University Medical College, New York, NY 10021.
authors.forename: P C
authors.initials: PC
authors.lastname: White
authors.forename: J
authors.initials: J
authors.lastname: Obeid
authors.forename: A K
authors.initials: AK
authors.lastname: Agarwal
authors.forename: G M
authors.initials: GM
authors.lastname: Tannin
authors.forename: H
authors.initials: H
authors.lastname: Nikkila
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics*; D008661:Metabolism, Inborn Errors / Q000201:enzymology; D008901:Mineralocorticoids / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation
chemical_list: D008901:Mineralocorticoids; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases