Multiple isoforms of the cortisol–cortisone shuttle

Abstract
Human plasma contains similar free concentrations of the active steroid cortisol and its inactive metabolite cortisone. Interconversion of cortisol and cortisone (or corticosterone and 11-dehydrocorticosterone in rats) has been recognized since the 1950s. Until recently it was thought that separate NADP/NADPH-dependent enzymes were responsible: 11β-dehydrogenase to convert cortisol to cortisone and 11β-reductase for the reverse reaction (Abramowitz, Branchaud & Murphy, 1982; Lakshmi & Monder, 1985). It is now known that both activities can be expressed from the same cDNA clone (Agarwal, Monder, Eckstein & White, 1989; Agarwal, TusieLuna, Monder & White, 1990), suggesting that a single 11β-hydroxysteroid dehydrogenase protein (11β-OHSD) catalyses both reactions. Recently, interest in the enzyme was stimulated by observations in patients with congenital 11β-dehydrogenase deficiency (the syndrome of apparent mineralocorticoid excess) (Ulick, Levine, Gunczler et al. 1979; Stewart, Corrie, Shackleton & Edwards, 1988) and in volunteers given the 11β-dehydrogenase inhibitors liquorice (Stewart, Valentino, Wallace et al