DIETARY ESTROGENIC ISOFLAVONES ARE POTENT INHIBITORS OF BETA-HYDROXYSTEROID DEHYDROGENASE OF P-TESTOSTERONII

The isoflavones daidzein, genistein, biochanin A and formononetin sele ctively inhibit the gamma-isozymes of mammalian alcohol dehydrogenase (ADH). Since gamma-ADH is the only ADH isoform that catalyzes 3 beta-h ydroxysteroid oxidation, it was conjectured that these isoflavones mig ht also inhibit other enzymes involved in 3 beta-hydroxysteroid metabo lism. P. testosteronii beta-hydroxysteroid dehydrogenase (beta-HSD) wa s used to evaluate this hypothesis. Indeed, all isoflavones that inhib it gamma-ADH were found to be potent inhibitors of beta-HSD. Both the 3 beta- and 17 beta-HSD activities of the enzyme are inhibited. Kineti c analyses with pregnenolone (3-beta-OH) and testosterone (17-beta-OH) as substrates reveal that daidzein and genistein inhibit beta-HSD com petitively with respect to the sterol substrates. Their K-i values are very similar and range from 0.013 to 0.02 mu M. These results suggest that isoflavones may exert some of their biological effects by modula ting activities of enzymes that metabolize steroids critical to hormon al and/or neuronal functions. (C) 1995 Academic Press, Inc.