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Abstract Title:

Bisphenol AF and bisphenol B exert higher estrogenic effects than bisphenol A via G protein-coupled estrogen receptor pathway.

Abstract Source:

Environ Sci Technol. 2017 Aug 31. Epub 2017 Aug 31. PMID: 28858478

Abstract Author(s):

Lin-Ying Cao, Xiao-Min Ren, Chuan-Hai Li, Jing Zhang, Wei-Ping Qin, Yu Yang, Bin Wan, Liang-Hong Guo

Article Affiliation:

Lin-Ying Cao

Abstract:

Numerous studies have indicated estrogenic disruption effects of bisphenol A (BPA) analogues. Previous mechanistic studies were mainly focused on their genomic activities on nuclear estrogen receptor pathway. However, their non-genomic effects through G protein-coupled estrogen receptor (GPER) pathway remain poorly understood. Here, using a SKBR3 cell-based fluorescence competitive binding assay, we found six BPA analogues bound to GPER directly, with bisphenol AF (BPAF) and bisphenol B (BPB) displaying much higher (~9-fold) binding affinity than BPA. Molecular docking also demonstrated the binding of these BPA analogues to GPER. By measuring calcium mobilization and cAMP production in SKBR3 cells, we found the binding of these BPA analogues to GPER lead to the activation of subsequent signaling pathways. Consistent with the binding results, BPAF and BPB presented higher agonistic activity than BPA with the lowest effective concentration (LOEC) of 10 nM. Moreover, based on the results of Boyden chamber and wound-healing assays, BPAF and BPB displayed higher activity in promoting GPER mediated SKBR3 cell migration than BPA with the LOEC of 100 nM. Overall, we found two BPA analogues BPAF and BPB could exert higher estrogenic effects than BPA via GPER pathway at nanomolar concentrations.

Study Type : In Vitro Study
Additional Links
Problem Substances : Bisphenol A : CK(685) : AC(178)

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Sayer Ji
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