hydroxysteroid dehydrogenase (11␤HSD) type 1 (11␤HSD1) enzyme is an NADP ϩdependent oxidoreductase, usually reductase, of major glucocorticoids. The NAD ϩ -dependent type 2 (11␤HSD2) enzyme is an oxidase that inactivates cortisol and corticosterone, conferring extrinsic specificity of the mineralocorticoid receptor for aldosterone. We reported that addition of a reducing agent to renal homogenates results in the monomerization of 11␤HSD2 dimers and a significant increase in NAD ϩ -dependent

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... icosterone conversion. Estrogenic effects on expression, dimerization, and activity of the kidney 11␤HSD1 and -2 enzymes are described herein. Renal 11␤HSD1 mRNA and protein expressions were decreased to very low levels by estradiol (E2) treatment of both intact and castrated male rats; testosterone had no effect. NADP ϩdependent enzymatic activity of renal homogenates from E2-treated rats measured under nonreducing conditions was less than that of homogenates from intact animals. Addition of 10 mM DTT to aliquots from these same homogenates abrogated the difference in NADP ϩ -dependent activity between E2-treated and control rats. In contrast, 11␤HSD2 mRNA and protein expressions were significantly increased by E2 treatment. There was a marked increase in the number of juxtamedullary proximal tubules stained by the antibody against 11␤HSD2 after the administration of E2. Notwithstanding, neither the total corticosterone and 11-dehydrocorticosterone excreted in the urine nor their ratio differed between E2and vehicle-treated rats. NAD ϩ -dependent enzymatic activity in the absence or presence of a reducing agent demonstrated that the increase in 11␤HSD2 protein was not associated with an increase in in vitro activity unless the dimers were reduced to monomers.