11-DEHYDROCORTICOSTERONE, A GLUCOCORTICOID METABOLITE, INHIBITS ALDOSTERONE ACTION IN TOAD BLADDER

The enzyme 11-beta-hydroxysteroid dehydrogenase (11-beta-OHSD) metabolizes glucocorticoid hormones and diminishes their ability to induce sodium transport. In these studies, we determined the location of this enzyme in toad bladder and assessed the biological role for its 11-dehydro end product. Employing a polyclonal antibody directed toward 11-beta-OHSD and immunofluorescence techniques, we located the enzyme in the epithelial cell layer of the toad bladder. Although corticosterone (10(-7) M) can partially suppress aldosterone (10(-7) M)-stimulated short-circuit current (SCC), a clear excess of corticosterone (10(-6) M) did not inhibit the aldosterone-induced (10(-8) M) rise in SCC (n = 6). The 11-dehydro product of corticosterone, 11-dehydrocorticosterone (compound A) added to the serosal bath suppressed aldosterone (10(-8) M) peak SCC (360 min) in a dose-dependent fashion reaching 46 +/- 5% of control values at 10(-5) M (n = 6; P < 0.001). Compound A (10(-5) M) in the mucosal bath also was capable of partially inhibiting the peak aldosterone rise in SCC to 63 +/- 7% of control values with aldosterone at 10(-8) M (n = 6; P < 0.01) and to 64 +/- 10% of control values with aldosterone at 10(-7) M (n = 9; P < 0.01). Compound A alone at 10(-5) M did not have any effect on SCC. Isolated toad bladders were not able to transform compound A (at 10(-8) and 10(-5) M) back to corticosterone. Thus the 11-dehydro end product of 11-beta-OHSD (compound A) may play a biologic role by regulating a compotent of mineralocorticoid-induced sodium transport.