INFLUENCE OF DIETARY-SODIUM ON THE RENAL ISOFORMS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE

Endogenous glucocorticoids are converted to their biologically inert 1 1-dehydroderivatives by isoforms of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). The low-K-m, NAD(+)-dependent renal isofo rm (Type 2) identified in the distal nephron protects mineralocorticoi d receptors from activation by endogenous glucocorticoids. The functio n of high-K-m, NADP(+)-dependent renal isoform (Type 1) is less well u nderstood. Since glucocorticoids may modulate sodium transport in rena l proximal tubules (Pi), we hypothesized that Type 1 activity in this segment may be regulated by dietary Na+. 11 beta-HSD activity was asse ssed in homogenates of canine PT by the conversion of cortisol to cort isone in the presence of NADP(+) 200 mu M. A high-Na+ diet for 4 days increased the V-max 4-fold, with no change in the Type 1 K-m (40 mEq/d ay Na+ diet: K-m 0.959 mu M, V-max 3.40 pmoles/min/mg protein versus 1 50 mEq/day Na+ diet: K-m 0.962 mu M V-max 14.8 pmoles/min/mg protein). Type 1 mRNA also rose in the salt repleted animals. The high-Na+ diet produced no detectable change in the Type 2 isoform enzyme kinetics a nd mRNA level. No reverse oxo-reductase activity was noted with either renal isoform. Thus, renal Type 1 11 beta-HSD can be regulated by die tary Na+ independent of changes in the renal Type 2 isoform.