RAT-LIVER 11-BETA-HYDROXYSTEROID DEHYDROGENASE COMPLEMENTARY DEOXYRIBONUCLEIC-ACID ENCODES OXOREDUCTASE ACTIVITY IN A MINERALOCORTICOID-RESPONSIVE TOAD BLADDER CELL-LINE

The mineralocorticoid receptor displays equal affinity for aldosterone and corticosterone. It has been proposed that aldosterone selectivity in vivo is achieved by the conversion of corticosterone into its inactive metabolite 11-dehydrocorticosterone by 11beta-hydroxysteroid dehydrogenase (11betaHSD). To test this hypothesis, we transfected rat liver 11betaHSD cDNA into TBM cells, a sodium-transporting cell line. These cells respond equally well to aldosterone and corticosterone, indicating that endogenous 11betaHSD is expressed at low levels in TBM cells. Although exogenous rat liver 11betaHSD was expressed at high levels in transfected cells, mineralocorticoid selectivity was not observed. By contrast, the biologically inactive 11-dehydrocorticosterone was readily converted into corticosterone, a potent agonist for sodium transport. Our results indicate that rat liver 11betaHSD behaves predominantly as a reductase in TBM cells. Another 11betaHSD isoform is likely to be responsible for the dehydrogenase reaction in aldosterone-responsive cells.