Cloning of the 11βHSD type II enzyme from human kidney

The enzyme 11β-hydroxysteroid dehydrogenase (11βHSD) converts glucocorticoids to receptor inactive metabolites. Two isoforms of the enzyme exist. 11βHSD1 is a low affinity NADP dependent enzyme, while 11βHSD2 is a high affinity NAD dependent species thought to be responsible for endowing specificity on the mineralocorticoid receptor and for protecting the fetus from high circulating levels of maternal glucocorticoids. We have recently cloned the human renal 11βHSD2 enzyme. In this report we show that 11βHSD2 potently inactivates the synthetic glucocorticoid dexamethasone, producing a single product thought to be the 11 -dehydrodexamethasone metabolite. Sequence analysis shows that the new isoform is a member of the short-chain alcohol dehydrogenase superfamily (SCAD), most closely related to 17βHSD2 and distantly related to 11βHSD1.