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.