Inhibition of 11 beta-hydroxysteroid dehydrogenase by gossypol and bioflavonoids.

The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) oxidizes hydrocortisone to inactive cortisone in the kidney and is an important regulator of renal K+ clearance. Gossypol, in clinical trials as an antifertility drug for men in China, was associated with episodes of hypokalemia. To learn whether gossypol and other structurally similar compounds in plants can inhibit 11 beta-OHSD activity, purified enzyme from rat liver and in human renal cortical microsomes was studied. Rat liver enzyme was inhibited by glycyrrhetinic acid > gossypol >> morin > quercetin >> rutin. Glycyrrhetinic acid, gossypol, and morin inhibited activity of the human kidney enzyme. Enzyme in microsomes from five human kidneys had an IC50 (S.D.) of 1.5 (1.2) mumol/L for glycyrrhetinic acid; enzyme in microsomes from six human kidneys had a 50% inhibitory doses of 147 (25) mumol/L for gossypol. Our observations indicate that gossypol and other compounds in plants can inhibit 11 beta-OHSD activity and may thereby increase K+ excretion.