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Toxicology. 2017 Jul 15;387:10-16. doi: 10.1016/j.tox.2017.06.007. Epub 2017 Jun 20.

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

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School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221000, China.
School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221000, China. Electronic address:


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.


Amino- and carboxyl-terminal interaction; Androgen receptor signaling; Bisphenol A; Nuclear receptor co-repressor; Silencing mediator for thyroid hormone receptor

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