Regulation of 11 beta-hydroxysteroid dehydrogenase enzymes by dietary sodium in the rat

11 beta-Hydroxysterold dehydrogenase enzymes (11 beta-HSD1, 11 beta-HSD2) r egulate access of adrenocorticosteroids to receptors. 11 beta-HSD2 is a deh ydrogenase that protects mineralocorticoid receptors from circulating gluco corticoid hormones, 11 beta-HSD1 is a reductase that promotes formation of active hormone in glucocorticoid-sensitive tissues. Here we investigate whe ther low or high sodium diets affect 11 beta-HSD enzyme activities and mRNA expression in liver and kidney tissues. 11 beta-HSD activity was measured as dehydrogenation of H-3-corticosterone by microsomes in the presence of N AD or NADP. In situ hybridisation techniques were used to assess expression of 11 beta-HSD1 mRNA (liver and kidney) and 11 beta-HSD2 mRNA (kidney). Di etary sodium did not affect 11 beta-HSD2 mRNA expression in collecting tubu les of the medulla: 11 beta-HSD1 mRNA in proximal tubules of the inner cort ex/outer medulla was lower after a high sodium diet. 11 beta-HSD1 mRNA in l iver was unaffected by treatment. Renal enzyme activity with NAD (11 beta-H SD2 cofactor) was lower following a high sodium diet (P < 0.05). In the pre sence of NADP (11 beta-HSD1 co-factor), neither renal nor hepatic activitie s were affected. Dietary sodium restriction appears to increase 11 beta-HSD activity by a non-genomic mechanism; this should enhance aldosterone speci ficity for mineralocorticoid receptors. 11 beta-HSD1 mRNA expression varies independent of enzyme activity and is not clearly related to altered gluco corticoid activity.