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 (IC 50 ) 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 µmol L -1 androstenedione), with an IC 50 ≥ 100 µmol L -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.

Hydroxysteroid Dehydrogenases – Localization, Function and Regulation in the Testis

“…These authors concluded that inhibition of 3 -HSD function is one of the possible mechanism through which xenoestrogens disturb spermatogenesis. In vitro studies on Leydig cells obtained from various mammals have revealed decrease in the activity and expression of 3 -HSD after OP, bisphenol A (BPA) and genistein administration (Hu et al, 2010;Kotula-Balak et al, 2011;Ye et al, 2011). Our study demonstrated that OP markedly disturbes morphology and steroidogenic function of the Leydig cells through direct effect on 3 -HSD expression and localization .…”

“…It is worth noting that the effect of EDCs on HSDs function can be diverse depending on the choice of animal species, age, routes of administration and dose levels. Studies of PogrmicMajkic et al (2010) have shown that in rat Leydig cells atriazine stimulated 17 -HSD, whereas other authors reported inhibition of these enzyme in rat and human microsomes treated with various xenoestrogens (Hu et al, 2010;Vaithinathan et al, 2008;Ye et al, 2011). Recently, it has also been found that antiandrogens such as tributylin, triclosan and flutamide modified HSDs expression in Leydig cells and microsomes of various mammals (Kim et al, 2008;Kumar et al, 2009;McVey & Cooke, 2003;Ohno et al, 2005;Ohsako et al, 2003).…”

Endocrine milieu and erectile dysfunction: is oestradiol–testosterone imbalance, a risk factor in the elderly?

“…In animal studies, correlations have already been made between phytoestrogen intake, androgen decrease and ED. 37,[65][66][67] In the light of this evidence, it is important to bridge the lacunae in the understanding of this sexual health threat to men through well-designed epidemiological and prevalence studies.…”

Natural Flavonoids in StAR Gene Expression and Testosterone Biosynthesis in Leydig Cell Aging

“…While these flavonoids might enhance StAR gene expression by reducing the transcriptional repressor DAX-1 protein, they might inhibit the positive effect of calciumdependent signaling on StAR gene expression; 2) Inhibitory effects of flavonoids on steroidogenic enzymes. It was reported that some of the flavonoids are able to inhibit activities of the enzymes involved in testosterone biosynthesis (Figueiroa et al, 2009;Hu et al, 2010). These inhibitory effects may reduce the efficacy of flavonoid-enhanced testosterone production; 3) Levels of cAMP in Leydig cells.…”