内科学
内分泌学
雄激素受体
促黄体激素
二氢睾酮
兴奋剂
化学
雄激素
睾酮(贴片)
作用机理
信号转导
受体
生物
生物化学
激素
医学
前列腺癌
癌症
体外
作者
Xinda Zhang,Xiaorong Zhang,Yanan Shi,Zhenzhong Zhang,Jun Wang,Shaoguo Ru,Hua Tian
出处
期刊:Chemosphere
[Elsevier]
日期:2024-02-01
卷期号:350: 141056-141056
标识
DOI:10.1016/j.chemosphere.2023.141056
摘要
Bisphenol S (BPS) exhibited inhibitory effects on androgen synthesis, but its target of action remains unclear. We investigated the effects of BPS exposure at environmentally relevant concentrations (1 μg/L, 10 μg/L and 100 μg/L) for 48 h on androgen synthesis in rat ovarian theca cells and explored the underlying mechanisms, target site and target molecule. The results showed that BPS exposure inhibited the transcript levels of steroidogenic genes and reduced the contents of androgen precursors, testosterone and dihydrotestosterone. BPS exposure decreased the phosphorylation levels of extracellular signal-related kinase 1/2 (ERK1/2), and the inhibitory effects of BPS on testosterone content and steroidogenic gene expression were blocked by ERK1/2 agonist LY2828360, suggesting that ERK1/2 signaling pathway mediates the inhibitory effects of BPS on androgen synthesis. BPS mainly accumulated on the cell membrane, impermeable BPS-bovine serum albumin exposure still inhibited androgen synthesis, BPS interacted with rat luteinizing hormone receptor (LHR) via formation of hydrogen bonds in the transmembrane region, and the inhibitory effects of BPS on ERK1/2 phosphorylation were blocked by luteinizing hormone (the natural agonist of LHR), indicating that LHR located on the cell membrane is the target of action of BPS. This paper provides a new elucidation of the mechanism of anti-androgenicity of BPS, especially for the non-genomic pathways.
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