持久的DDT代谢物p,p'-DDE是一种强大的雄激素受体对手
W R Kelce1, C R Stone, S C Laws
1Reproductive Toxicology Branch, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Nature
|June 15, 1995
概括
环境化学物质p,p'-DDE是一种DDT代谢物,没有显著的结合雌激素受体. 相反,它抑制了雄激素受体活性,这表明男性发育异常的新机制.
科学领域:
- 内分泌学 在内分泌学.
- 环境毒理学环境毒理学
- 生殖生物学 生殖生物学
背景情况:
- 野生动物和人类的男性性发育异常的报告与像DDT这样的雌激素化学物质的引入有关.
- 现型变化通常归因于雌激素受体调解,但抑制雄激素受体通路也是一种可能性.
研究的目的:
- 研究DDT代谢物p,p'-DDE影响男性性发育的机制.
- 为了确定p,p'-DDE是否与雌激素或雄激素受体相互作用.
主要方法:
- 评估了p,p'-DDE与雌激素受体的结合能力.
- 研究了p,p'-DDE对雄激素与雄激素受体结合的作用.
- 在暴露于p,p'-DDE.的雄性大鼠中评估了雄激素诱导的转录活性和作用.
主要成果:
- p,p'-DDE对雌激素受体具有最小的结合亲和力.
- p,p'-DDE显著抑制了与雄激素受体的雄激素结合.
- 在发育,青春期和成年雄性大鼠中,androgen诱导的转录活性和作用被p,p '-DDE抑制.
结论:
- 这些发现表明,p,p'-DDE对男性性发育的干扰可能是通过雄激素受体而不是雌激素受体进行的.
- 这项研究发现了环境化学物质引起的生殖异常的新机制.
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