CLONING OF THE 11-BETA-HSD TYPE-II ENZYME FROM HUMAN KIDNEY

The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) converts glucocorticoids to receptor inactive metabolites. Two isoforms of the enzyme exist. 11 beta HSD1 is a low affinity NADP dependent enzyme, w hile 11 beta HSD2 is a high affinity NAD dependent species thought to be responsible for endowing specificity on the mineralocorticoid recep tor and for protecting the fetus from high circulating levels of mater nal glucocorticoids. We have recently cloned the human renal 11 beta H SD2 enzyme. In this report we show that 11 beta HSD2 potently inactiva tes the synthetic glucocorticoid dexamethasone, producing a single pro duct thought to be the 11-dehydrodexamethasone metabolite. Sequence an alysis shows that the new isoform is a member of the short-chain alcoh ol dehydrogenase superfamily (SCAD), most closely related to 17 beta H SD2 and distantly related to 11 beta HSD1.