Effects of genistein and equol on human and rat testicular 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase 3 activities.

The objective of the present study was to investigate the effects of genistein and equol on 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase 3 (17beta-HSD3) in human and rat testis microsomes. These enzymes (3beta-HSD and 17beta-HSD3), along with two others (cytochrome P450 side-chain cleavage enzyme and cytochrome P450 17alpha-hydroxylase/17-20 lyase), catalyze the reactions that convert the steroid cholesterol into the sex hormone testosterone. Genistein inhibited 3beta-HSD activity (0.2 micromol L(-1) pregnenolone) with half-maximal inhibition or a half-maximal inhibitory concentration (IC(50)) of 87 +/- 15 (human) and 636 +/- 155 nmol L(-1) (rat). Genistein's mode of action on 3beta-HSD activity was competitive for the substrate pregnenolonrge and noncompetitive for the cofactor NAD(+). There was no difference in genistein's potency of 3beta-HSD inhibition between intact rat Leydig cells and testis microsomes. In contrast to its potent inhibition of 3beta-HSD, genistein had lesser effects on human and rat 17beta-HSD3 (0.1 micromol L(-1) androstenedione), with an IC(50) >or= 100 micromol L(-1). On the other hand, equol only inhibited human 3beta-HSD by 42%, and had no effect on 3beta-HSD and 17beta-HSD3 in rat tissues. These observations imply that the ability of soy isoflavones to regulate androgen biosynthesis in Leydig cells is due in part to action on Leydig cell 3beta-HSD activity. Given the increasing intake of soy-based food products and their potential effect on blood androgen levels, these findings are greatly relevant to public health.