多重核受体调节的内分泌干扰效应:对双醇诱导的RARα和ERα信号通路之间的交叉声的案例研究
Jiahui Su1, Qian S Liu2, Xiaoxi Yang2
1State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China.
Journal of hazardous materials
|June 25, 2025
概括
像双醇这样的新兴化学物质通过影响雌激素受体α (ERα) 和视网膜酸受体α (RARα) 信号来破坏内分泌平衡. 这项研究揭示了ERα和RARα通路之间的对抗性交叉,影响细胞增殖.
科学领域:
- 内分泌学 在内分泌学.
- 分子毒理学 分子毒理学
- 细胞生物学 细胞生物学
背景情况:
- 内分泌平衡依赖于复杂的核受体 (NR) 调节.
- 新出现的化学物质可以通过与多个NRs相互作用来破坏这一过程.
- 雌激素受体α (ERα) 和视网膜酸受体α (RARα) 之间的交叉是关键的关注领域.
研究的目的:
- 为了研究六种双甲类同类物质的雌激素和视网类活性.
- 探索由双醇调节的ERα和RARα信号通路之间的交叉声.
- 为了阐明这种交叉对人类乳腺癌 (MCF-7) 细胞行为的影响.
主要方法:
- 在体外和内测试被用于选双相似物以检测ERα和RARα活性.
- 双BPB和BPAF由于具有较高的结合亲缘关系而被选择进行进一步研究.
- 使用MCF-7细胞检查ERα和RARα调制对细胞增殖和基因转录的影响.
主要成果:
- 两个ERα和RARα信号通路都被双相似物调节.
- RARα激动性和对抗性影响双醇激活的ER-依赖细胞增殖和基因转录.
- ERα激动性抑制了双醇介导的RARα信号传递,而ERα对抗性则增强了它.
- 观察到ERα和RARα信号之间的对抗性交叉声.
结论:
- 双可以通过ERα激动抑制RARα信号传递,突出显示复杂的NR相互作用.
- 这项研究揭示了ERα和RARα信号通路之间的对抗性交叉声.
- 了解NR交叉对评估具有多个NR亲属性的化学物质对内分泌干扰的影响至关重要.
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