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

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• 作者：Shereen Cynthia D’ ; Cruz^a ; Rajamanickam Jubendradass^a ; Mannu Jayakanthan^b ; Sivaraj Judith Amala Rani^a ; Premendu Prakash Mathur^a ; ^b ; ^{ppmathur.bbm@pondiuni.edu.in}
• 关键词：Bisphenol A ; Testis ; Insulin signaling ; Glucose transporter-2 ; Steroidogenesis
• 刊名：Food and Chemical Toxicology
• 出版年：2012
• 期刊代码：20_02786915
• 类别：pha
• 出版时间：March-April, 2012
• 卷：50
• 期：3-4
• 页码：1124-1133
• 文件大小：1902 K

摘要

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 渭g/kg body weight/day for 45 days. A positive control was maintained by administering 17-尾-estradiol (50 渭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-尾-hydroxysteroid dehydrogenase (3尾-HSD), 17-尾-hydroxysteroid dehydrogenase (17尾-HSD), Steroidogenic Acute Regulatory Protein (StAR) and testosterone were also observed. Molecular docking of BPA, 17-尾-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.