Inhibition of human and rat testicular steroidogenic enzyme activities by bisphenol A

Bisphenol A (BPA) is a potential endocrine disruptor. It has been shown that it reduces serum testosterone level in rodents after exposure. However, the mechanism is unclear. The object of the present study is to investigate the effects of BPA on human and rat steroidogenic enzymes including P450 17 alpha-hydroxylase/17,20-lyase (CYP17A1), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase 3 (17 beta-HSD3). Human and rat testis microsomes were exposed to various concentrations of BPA (10(-8)-10(-4) M). BPA inhibited human and rat 3 beta-HSD, CYP17A1 and 17 beta-HSD3 activities. The half maximal inhibitory concentrations (IC(50)s) of BPA for human and rat testis 3 beta-HSD were 7.92 +/- 1.03 and 26.49 +/- 3.03 mu M (200 mu M pregnenolone), respectively. The IC(50)s for human and rat CYP17A1 (1 mu M progesterone) were 18.99 +/- 3.75 and 64.67 +/- 4.04 mu M, respectively. BPA was a weak HSD17B3 inhibitor with IC(50)s of about 100 mu M (200 nM androstenedione). BPA also concentration-dependently inhibited testosterone production by rat Leydig cells. In conclusion, BPA is an inhibitor for 3 beta-HSD, CYP17A1 and 17 beta-HSD3. Human 3 beta-HSD and CYP17A1 are more sensitive to BPA than rat 3 beta-HSD and CYP17A1. (C) 2011 Elsevier Ireland Ltd. All rights reserved.