Bisphenol A impairs insulin signaling and glucose homeostasis and decreases steroidogenesis in rat testis: An in vivo and in silico study

Bisphenol A (BPA) is a potential endocrine disruptor and testicular toxicant. Recently, we have reported that exposure to BPA increases plasma insulin and glucose levels and decreases the levels of glycolytic enzymes, glucose transporter-8 (GLUT-8) and insulin receptor substrate-2 (IRS-2) in rat testis. In the present study we sought to investigate the effects of low doses of BPA on insulin signaling molecules, glucose transporter-2 (GLUT-2) and steroidogenesis in rat testis. BPA was administered to rats by oral gavage at doses of 0.005, 0.5, 50 and 500 mu g/kg body weight/day for 45 days. A positive control was maintained by administering 17-beta-estradiol (50 mu g/kg body weight/day). Decreased levels of insulin, insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI-3 kinase) and GLUT-2 were observed in rat testis following BPA administration. Dose-dependent decrease in the activities of antioxidant enzymes, 3-beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17-beta-hydroxysteroid dehydrogenase (17 beta-HSD), Steroidogenic Acute Regulatory Protein (StAR) and testosterone were also observed. Molecular docking of BPA, 17-beta-estradiol, cytochalasin B and glucose with GLUT-2 and GLUT-8 revealed the higher binding affinity of BPA with GLUT-2 and GLUT-8. Thus, BPA impairs insulin signaling and glucose transport in rat testis which could consequently lead to impairment of testicular functions. (C) 2011 Elsevier Ltd. All rights reserved.