GENETIC-ANALYSIS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) catalyzes the inte rconversion of cortisol and cortisone. This activity is postulated to protect the Type T (mineralocorticoid) receptor from excessive concent rations of cortisol, allowing aldosterone to function as a mineralocor ticoid. An enzyme with 11 beta-OHSD activity was isolated from rat liv er and the corresponding rat and human cDNA and genomic clones isolate d This enzyme is a member of the short-chain dehydrogenase family. Usi ng site-directed mutagenesis, it was demonstrated that the amino termi nus and two highly conserved residues, Tyr-179 and Lys-183, are requir ed for enzymatic function. Examination of patients with apparent miner alocorticoid excess, a syndrome of juvenile hypertension thought to re present 11 beta-OHSD deficiency, did not reveal any mutations in the H SD11 gene. This disorder may involve an additional enzyme with 11 beta -OHSD activity or possibly another cortisol metabolizing enzyme.