Bisphenol S causes excessive estrogen synthesis by activating FSHR and the downstream cAMP/PKA signaling pathway

作者：Xiaorong Zhang, Xinda Zhang, Zhenzhong Zhang, Yijiao Shi, Jun Wang, Shaoguo Ru, Hua Tian · 发表于：Communications Biology · 年份：2024 · DOI：10.1038/s42003-024-06449-2 · 被引用次数：14 · 研究领域：Effects and risks of endocrine disrupting chemicals、Estrogen and related hormone effects、Toxic Organic Pollutants Impact

Estrogen excess in females has been linked to a diverse array of chronic and acute diseases. Emerging research shows that exposure to estrogen-like compounds such as bisphenol S leads to increases in 17β-estradiol levels, but the mechanism of action is unclear. The aim of this study was to reveal the underlying signaling pathway-mediated mechanisms, target site and target molecule of action of bisphenol S causing excessive estrogen synthesis. Human ovarian granulosa cells SVOG were exposed to bisphenol S at environmentally relevant concentrations (1 μg/L, 10 μg/L, and 100 μg/L) for 48 h. The results confirms that bisphenol S accumulates mainly on the cell membrane, binds to follicle stimulating hormone receptor (FSHR) located on the cell membrane, and subsequently activates the downstream cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathway, leading to enhanced conversion of testosterone to 17β-estradiol. This study deepens our knowledge of the mechanisms of environmental factors in pathogenesis of hyperestrogenism.