Inhibitory effects of gossypol on corticosteroid 11-beta-hydroxysteroid dehydrogenase from guinea pig kidney: a possible mechanism for causing hypokalemia.

Inhibition of 11-beta-hydroxysteroid dehydrogenase (11-beta-OHSD) in the kidney can cause excess mineralocorticoid effect and hypokalemia. To find out if gossypol, a potential oral contraceptive for men that has been associated with cases of hypokalemia, inhibits this enzyme, its effect on guinea pig kidney was studied. Working with microsomes from the kidney cortex, and using corticosterone as the substrate, racemic gossypol was found to be a competitive inhibitor of 11-beta-OHSD with a Ki of 67 +/- 5 microM. The (+) enantiomer was a little more potent than the (-) enantiomer. Microsomes from the kidneys of animals given gossypol for 2 weeks had lower enzyme activities than saline-treated animals. Microsomes from a strain of hairless guinea pigs had lower intrinsic enzyme activity than the normal animals. We conclude that there is genetic variation in the activity of this enzyme and that it can be inhibited by gossypol.