Effects of glycyrrhetinic acid and its derivatives on delta 4-5 alpha- and 5 beta-reductase in rat liver.

The effect of glycyrrhetinic acid (GA) and its derivatives on delta 4-5 alpha- and 5 beta-reduction of cortisol, aldosterone and testosterone was investigated on rat liver preparations. In vitro studies demonstrated that GA and its derivatives inhibited 5 beta-reduction to a much greater extent than 5 alpha-reduction. When GA or glycyrrhizin (GL) were administered, 5 beta-reductase activity was significantly suppressed. On the contrary, 5 alpha-reductase was markedly increased though its meachnism remains to be clarified. In human beings 5 beta-reductase is quantitatively the major enzyme and plays an important role in the regulation of cortisol and aldosterone metabolism. Thus from the studies presented here, it can be presumed that the suppression of 5 beta-reductase activity by GA or GL administration may delay the clearance of corticosteroids and prolong the biological half-life of cortisol resulting in the synergism of these steroids and GA or GL.