氯菊酯对雄激素受体与共激活因子 ARA70 和 ARA55 相互作用的抑制作用。
Inhibitory Effects of Cypermethrin on Interactions of the Androgen Receptor with Coactivators ARA70 and ARA55.
机构信息
School of Public Health, Xuzhou Medical University, Xuzhou 221000, Jiangsu, China.
出版信息
Biomed Environ Sci. 2020 Mar 20;33(3):158-164. doi: 10.3967/bes2020.022.
OBJECTIVE
The purpose of this study was to investigate the anti-androgenic mechanism of cypermethrin involving coactivators.
METHODS
Mammalian two-hybrid assays were performed to study the effects of cypermethrin on interactions of the androgen receptor (AR) with the coactivators androgen receptor-associated protein 70 (ARA70) and androgen receptor-associated protein 55 (ARA55).
RESULTS
The results showed that AR-ARA70 and AR-ARA55 interactions were remarkably enhanced by dihydrotestosterone (DHT, ≤ 0.05). Cypermethrin inhibited DHT-induced AR-ARA70 and AR-ARA55 interactions significantly ( ≤ 0.05).
CONCLUSION
The study indicates that cypermethrin exhibits inhibitory effects on AR transcription associated with repression of AR-ARA70 and AR-ARA55 interactions in a ligand-dependent manner. The data show novel anti-androgenic mechanisms of cypermethrin that contribute to male reproductive toxicology.
目的
本研究旨在探讨氯菊酯通过共激活子对雄激素受体的抗雄激素作用机制。
方法
采用哺乳动物双杂交实验，研究氯菊酯对雄激素受体（AR）与共激活子雄激素受体相关蛋白 70（ARA70）和雄激素受体相关蛋白 55（ARA55）相互作用的影响。
结果
结果表明，二氢睾酮（DHT，≤0.05）可显著增强 AR-ARA70 和 AR-ARA55 的相互作用。氯菊酯显著抑制 DHT 诱导的 AR-ARA70 和 AR-ARA55 相互作用（≤0.05）。
结论
本研究表明，氯菊酯通过抑制 AR-ARA70 和 AR-ARA55 的相互作用，从而抑制与 AR 转录相关的活性，表现出配体依赖性的抗雄激素作用。这些数据为氯菊酯的雄性生殖毒性提供了新的抗雄激素作用机制。
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