GLYCYRRHIZIN INDUCES MINERALOCORTICOID ACTIVITY THROUGH ALTERATIONS IN CORTISOL METABOLISM IN THE HUMAN KIDNEY

It has been suggested that the mineralocorticoid action of glycyrrhizin is caused by a defect in the conversion of cortisol to cortisone through inhibition of the enzyme 11 beta-dehydrogenase (11 beta-DH). We investigated the functional significance of the inhibition of this enzyme as a mechanism of the mineralocorticoid action of glycyrrhizin. Eighteen healthy volunteers were divided into three groups of six and treated as follows: (1) 225 mg glycyrrhizin/day, (2) 0.1 mg 9alpha-fluorocortisol (FC)/day and (3) 225 mg glycyrrhizin and 1.5 mg dexamethasone/day, all of which were given for 7 days. The administration of glycyrrhizin or FC induced a similar mineralocorticoid effect; specifically, suppression of plasma renin activity, hypokalaemia and kaliuresis. During the concomitant administration of glycyrrhizin and dexamethasone, however, these mineralocorticoid effects were significantly attenuated. During the administration of glycyrrhizin, urinary excretion of cortisol increased without change in the plasma levels of cortisol, while both plasma level and uninary excretion of cortisone decreased. Changes in cortisol metabolism were not observed during the administration of FC. These results demonstrated the functional significance of the inhibition of 11 beta-DH in the mineralocorticoid activity of glycyrrhizin in man.