Anti-androgenic mechanisms of Bisphenol A involve androgen receptor signaling pathway.

Autor: Wang H; School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221000, China., Ding Z; School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221000, China., Shi QM; School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221000, China., Ge X; School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221000, China., Wang HX; School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221000, China., Li MX; School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221000, China., Chen G; School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221000, China., Wang Q; School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221000, China., Ju Q; School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221000, China., Zhang JP; School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221000, China., Zhang MR; School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221000, China., Xu LC; School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221000, China. Electronic address: lichunxu2002@163.com.
Jazyk: angličtina
Zdroj: Toxicology [Toxicology] 2017 Jul 15; Vol. 387, pp. 10-16. Date of Electronic Publication: 2017 Jun 20.
DOI: 10.1016/j.tox.2017.06.007
Abstrakt: We have shown Bisphenol A (BPA) acts as an androgen receptor (AR) antagonist in the previous study. However, the mechanisms underlying anti-androgenic effects of BPA remain unclear. The objective of this study was to explore whether the AR signaling was involved in AR antagonism of BPA. The Cell Counting Kit-8 (CCK-8) assay and Real-Time Cell Analysis (RTCA) iCELLigence system were applied to analyze the mouse Sertoli cell TM4 proliferation. The mammalian two-hybrid assays were performed to investigate the effects of BPA on the AR amino- and carboxyl-terminal regions (N/C) interaction and the interactions of the AR with steroid receptor coactivator-1 (SRC-1), co-repressors including silencing mediator for thyroid hormone receptors (SMRT) and nuclear receptor co-repressor (NCoR). BPA exposure resulted in decreased TM4 cell proliferation. BPA inhibited the AR N/C interaction significantly. Furthermore, BPA enhanced the interactions of AR-SMRT and AR-NCoR significantly. In conclusion, these data suggest BPA inhibits Sertoli cell proliferation due to its anti-androgenic actions. The mechanisms responsible for AR antagonism of BPA involve inhibiting the AR N/C interaction and enhancing the interactions of AR-SMRT and AR-NCoR. The data uncover novel anti-androgenic mechanisms by which BPA antagonizes AR signaling, contributing to Sertoli cell proliferation suppression and male reproductive toxicology.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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