Dietary estrogenic isoflavones are potent inhibitors of beta-hydroxysteroid dehydrogenase of P. testosteronii.

The isoflavones daidzein, genistein, biochanin A and formononetin selectively inhibit the gamma-isozymes of mammalian alcohol dehydrogenase (ADH). Since gamma-ADH is the only ADH isoform that catalyzes 3 beta-hydroxysteroid oxidation, it was conjectured that these isoflavones might also inhibit other enzymes involved in 3 beta-hydroxysteroid metabolism. P. testosteronii beta-hydroxysteroid dehydrogenase (beta-HSD) was used to evaluate this hypothesis. Indeed, all isoflavones that inhibit 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. Kinetic analyses with pregnenolone (3-beta-OH) and testosterone (17-beta-OH) as substrates reveal that daidzein and genistein inhibit beta-HSD competitively with respect to the sterol substrates. Their Ki values are very similar and range from 0.013 to 0.02 microM. These results suggest that isoflavones may exert some of their biological effects by modulating activities of enzymes that metabolize steroids critical to hormonal and/or neuronal functions.