CHARACTERISTICS AND REGULATION OF 11 BETA-HYDROXYSTEROID DEHYDROGENASE OF PROXIMAL AND DISTAL NEPHRON

Enzymatic properties of the enzyme 11 beta-hydroxysteroid dehydrogenas e (11-HSD), which confers mineralocorticoid selectivity, have been exp lored in the aldosterone-sensitive collecting duct (CCD) and the aldos terone-insensitive Pars Recta (PR) of the rat kidney. After incubation of freshly isolated tubular segments with [H-3]corticosterone (H-3-B) or [H-3]dehydrocorticosterone (H-3-A), the rate of transformation of H-3-B into H-3-A (dehydrogenase activity), or the reverse reaction (re ductase activity) were measured by HPLC. V-max for dehydrogenase activ ity was found to be 8- to 10-fold higher in CCD than PR. The enzyme fu nctions over a very wide range (0.1-5000 nM) of corticosterone concent ration. In CCD, enzyme kinetics suggest either the presence of two 11- HSD forms, differing by their affinity for corticosterone, or complex kinetics. Addition of NAD or NADP to permeabilized tubules revealed th at dehydrogenase activity is NAD-dependent in CCD and NADP-dependent i n PR. Cofactor addition was ineffective in intact tubules. CCD exhibit ed an exclusive dehydrogenase activity, whereas in PR dehydrogenase an d reductase activity were found. Na regulation of dehydrogenase activi ty could be evidenced in adrenalectomized rats receiving or not aldost erone, corticosterone or dexamethasone, for 2 h, 3 days or 4 days. We conclude that 11-HSD in the CCD and PR differs by its V-max and cofact or dependence. Corticosteroid hormones do not influence 11-HSD activit y.