Assessing Hormone Receptor Activities of Pyrethroid Insecticides and Their Metabolites in Reporter Gene Assays
Assessing Hormone Receptor Activities of Pyrethroid Insecticides and Their Metabolites in Reporter Gene Assays
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在报告基因测定中评估拟除虫菊酯杀虫剂及其代谢物的激素受体活性
DOI：
10.1093/toxsci/kfq120
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发表时间：
2010-07-01
影响因子：
3.8
通讯作者：
Wang, Xinru
中科院分区：
文献类型：
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作者：
Du, Guizhen;Shen, Ouxi;Wang, Xinru
拟除虫菊酯杀虫剂是全球最常用的杀虫剂，疑似干扰内分泌的化学物质。但它们与激素受体的相互作用仍不清楚。本研究旨在评估和比较激素受体（雌激素受体[ER]、雄激素受体[AR]和甲状腺激素受体[TR]）活性（环丙菊酯、氟氯氰菊酯、三氟氯氰菊酯、氯氰菊酯、溴氰菊酯、醚菊酯、氰戊菊酯、氯菊酯和胺菊酯）及其代谢产物（3-（2，2-二氯乙烯基）-2，2-二甲基环丙烯羧酸[DCCA]和3-苯氧基苯甲酸[3-PBA]）。在所测的H类化合物中，有4个化合物表现出很弱的雌激素受体激动活性，6个化合物表现出抗雌激素活性，其中三氟氯氰菊酯和DCCA分别具有最强的雌激素活性和抗雌激素活性。有7个化合物对AR有拮抗作用，其中氟氯氰菊酯和溴氰菊酯对AR的拮抗作用较强。在TR试验中，除DCCA外，所有供试化合物均表现出拮抗作用。在这项研究中，我们提供的证据表明，各种拟除虫菊酯及其代谢产物可能会破坏多种核激素受体的功能，从而有可能影响人类的内分泌和生殖系统。
Pyrethroid insecticides, the most commonly used insecticides worldwide, are suspected endocrine-disrupting chemicals. But their interactions with hormone receptors are still unclear. The present study intended to evaluate and compare the hormone receptor (estrogen receptor [ER], androgen receptor [AR], and thyroid hormone receptor [TR]) activities of nine pyrethroids (cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, deltarnethrin, etofenprox, fenvalerate, permethrin, and tetramethrin) and their metabolites (3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropne carboxylic acid [DCCA] and 3-phenoxybenzoic acid [3-PBA]) using receptor-mediated luciferase reporter gene assays. Of the H compounds tested, four showed very weak ER agonistic activities and six displayed antiestrogenic effects, among which cyhalothrin and DCCA possessed the most potent estrogenic and antiestrogenic activity respectively. Antagonistic effects to AR were found in 7 compounds, with cyfluthrin and deltamethrin exhibiting stronger AR antagonistic capacity. In the TR assay, all of tested chemicals except DCCA showed antagonistic effects. In this study, we provided evidence that a variety of pyrethroids and their metabolites might disrupt the function of multiple nuclear hormone receptors and thus have the potentials to affect the endocrine and the reproductive systems in humans.