title: Anti-androgen effects of cypermethrin on the amino- and carboxyl-terminal interaction of the androgen receptor.
abstract: The pyrethroid insecticide, cypermethrin has been demonstrated to be an environmental anti-androgen in the androgen receptor (AR) reporter gene assay. The amino- and carboxyl-terminal (N/C) interaction is required for transcription potential of the AR. In order to characterize the anti-androgen effects of cypermethrin involved in the N/C interaction of AR, the mammalian two-hybrid assay has been developed in the study. The fusion vectors pVP16-ARNTD, pM-ARLBD and the pG5CAT Reporter Vector were cotransfected into the CV-1 cells. The assay displayed appropriate response to the potent, classical AR agonist 5α-dihydrotestosterone (DHT) and known AR antagonist nilutamide. The N/C interaction was induced by DHT from 10(-11)M to 10(-5)M in a dose-dependent manner. Nilutamide did not activate N/C interaction, while inhibited DHT-induced AR N/C interaction at the concentrations from 10(-7)M to 10(-5)M. Treatment of CV-1 cells with cypermethrin alone did not activate the reporter CAT. Cypermethrin significantly decreased the DHT-induced reporter CAT expression at the higher concentration of 10(-5)M. The mammalian two-hybrid assay provides a promising tool both for defining mechanism involved in AR N/C interaction of EDCs and for screening of chemicals with androgen agonistic and antagonistic activities. Cypermethrin exhibits inhibitory effects on the DHT-induced AR N/C interaction, while the potency is weaker than that of nilutamide.
authors.affiliation: School of Public Health, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu 221002, China.
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Hu
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Pan
authors.forename: Jin-Peng
authors.initials: JP
authors.lastname: Zhang
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Xu
mesh_terms: D000726:Androgen Antagonists / Q000633:toxicity; D059002:Androgen Receptor Antagonists / Q000633:toxicity*; D002460:Cell Line; D013196:Dihydrotestosterone / Q000494:pharmacology; D006801:Humans; D048289:Imidazolidines / Q000494:pharmacology; D007306:Insecticides / Q000633:toxicity*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011722:Pyrethrins / Q000633:toxicity*; D011944:Receptors, Androgen / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D020798:Two-Hybrid System Techniques
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D048289:Imidazolidines; D007306:Insecticides; D011722:Pyrethrins; D011944:Receptors, Androgen; D011994:Recombinant Proteins; D013196:Dihydrotestosterone; C017160:cypermethrin; C021277:nilutamide