八甲基循环四西洛干 (D4) 缺乏通过雌激素通路的内分泌干扰潜力
Christopher J Borgert1, Lyle D Burgoon2
1Applied Pharmacology and Toxicology, Inc., and Department of Physiological Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA. cjborgert@apt-pharmatox.com.
Archives of toxicology
|February 20, 2025
概括
八甲基循环四西洛 (D4) 并不是一种雌激素内分泌干扰剂. 它的不良影响可能是由于非内分泌机制,如细胞膜破坏,而不是雌激素受体相互作用.
科学领域:
- 毒理学 毒理学 毒理学
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 八甲基循环四西洛 (D4) 是一种单体,具有备受争议的内分泌干扰特性.
- 一些研究表明D4是基于查试验的雌激素内分泌干扰剂 (EDC),而另一些研究则将影响归因于系统性毒性.
研究的目的:
- 解决关于D4的雌激素活性的相互矛盾的解释.
- 在分子,生化和生理层面研究D4与雌激素受体α (ERα) 的相互作用.
主要方法:
- 动物生理效应的证据权重 (WoE) 方法.
- 药理学计算以评估D4和17β-雌激醇 (E2) 的ERα占用率.
- 分子对接模拟以评估D4与ERα的结合.
主要成果:
- 发现D4的雌激素作用在分子,生化和生理上是不可思议的.
- 查试验结果不支持D4作为一种雌激素EDC.
- 动物的不良影响可能是高剂量,对细胞膜的物理化学影响的次要原因.
结论:
- D4不是一种雌激素的内分泌干扰物.
- 以前关于雌激素活性的说法是基于对查数据的错误解释.
- 观察到的不良反应可以通过非内分泌,剂量依赖的机制更好地解释.
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