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

Abstract

The objective of the present study was to investigate the effects of genistein and equol on 3Β-hydroxysteroid dehydrogenase (3Β-HSD) and 17Β-hydroxysteroid dehydrogenase 3 (17Β-HSD3) in human and rat testis microsomes. These enzymes (3Β-HSD and 17Β-HSD3), along with two others (cytochrome P450 side-chain cleavage enzyme and cytochrome P450 17α-hydroxylase/17-20 lyase), catalyze the reactions that convert the steroid cholesterol into the sex hormone testosterone. Genistein inhibited 3Β-HSD activity (0.2 μmol L-1 pregnenolone) with half-maximal inhibition or a half-maximal inhibitory concentration (IC50) of 87±15 (human) and 636±155 nmol L-1 (rat). Genistein's mode of action on 3Β-HSD activity was competitive for the substrate pregnenolonrge and noncompetitive for the cofactor NAD +. There was no difference in genistein's potency of 3Β-HSD inhibition between intact rat Leydig cells and testis microsomes. In contrast to its potent inhibition of 3Β-HSD, genistein had lesser effects on human and rat 17Β-HSD3 (0.1 mol L-1 androstenedione), with an IC 50±100 molL-1. On the other hand, equol only inhibited human 3Β-HSD by 42%, and had no effect on 3Β-HSD and 17Β-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 3Β-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. © 2010 AJA, SIMM & SJTU All rights reserved.