3-MONOGLUCURONYL-GLYCYRRHETINIC ACID IS A MAJOR METABOLITE THAT CAUSES LICORICE-INDUCED PSEUDOALDOSTERONISM

18 beta-Glycyrrhetinic acid (GA) has been thought to be one of the maj or metabolites that causes licorice-induced pseudoaldosteronism. Howev er, we found no difference in the blood level of GA between the patien ts with and without pseudoaldosteronism. We measured the blood concent ration of 3 beta-D-(monoglucuronyl)18 beta-glycyrrhetinic acid (3MGA), another metabolite of 3 beta-D-diglucuronyl-18 beta-glycyrrhetinic ac id (glycyrrhizin), by high performance liquid chromatography and found an increased concentration of 3MGA in 10 patients with licorice-induc ed pseudoaldosteronism, but not in 11 patients without pseudoaldostero nism. To investigate whether 3MGA can inhibit 11 beta-hydroxysteroid d ehydrogenase, we incubated rat renal microsome with or without 3MGA an d measured the conversion rate of [H-3]cortisol to [H-3]cortisone. 3MG A was found to be a potent inhibitor of 11 beta-hydroxysteroid dehydro genase, allowing cortisol to exert its full mineralocorticoid effects. These results suggest that licorice-induced pseudoaldosteronism is du e to an increased concentration of 3MGA, but not GA, in the circulatin g blood of these patients.