title: Anti-androgen effects of the pyrethroid pesticide cypermethrin on interactions of androgen receptor with corepressors.
abstract: To clarify whether the mechanism of androgen receptor (AR) antagonism of the pyrethroid pesticide cypermethrin associates with the interactions between the AR and corepressors silencing mediator for thyroid hormone receptors (SMRT) and nuclear receptor corepressor (NCoR), we have developed the mammalian two-hybrid assays. The AR N-terminal domain 1-660 amino acid residues were subcloned into the plasmid pVP16 to construct VP16-ARNTD. The C-terminal receptor interaction domains (RIDs) of SMRT and NCoR were used to construct pM-SMRT and pM-NCoR. The constructed vectors pVP16-ARNTD, pM-SMRT or pM-NCoR, the reporter pG5CAT and the control pCMVβ were cotranfected into the CV-1 cells. The cells were treated with cypermethrin at the indicated concentrations. The AR N terminus interacted with RIDs of SMRT and NCoR. The interactions between the AR and corepressors SMRT and NCoR were enhanced by cypermethrin, and the significant enhancement was detected at the concentration of 10(-5)M. The mammalian two-hybrid assays demonstrate the utility to detect the interactions of the AR with SMRT and NCoR. Cypermethrin functions as an anti-androgen by enhancing the associations of the AR with SMRT and NCoR. We provide a novel mechanism in anti-androgen action of cypermethrin associated with the recruitment of SMRT and NCoR to AR.
authors.affiliation: School of Public Health, Xuzhou Medical College, Xuzhou, 84 West Huai-hai Road, Xuzhou, Jiangsu 221002, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Pan
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Ya-Peng
authors.initials: YP
authors.lastname: Liu
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Xu
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Li
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Hu
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.forename: Jin-Peng
authors.initials: JP
authors.lastname: Zhang
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Zhang
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Yu
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Zhou
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Zhou
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Xu
mesh_terms: D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D000882:Haplorhini; D007306:Insecticides / Q000633:toxicity*; D056971:Nuclear Receptor Co-Repressor 1 / Q000378:metabolism*; D056985:Nuclear Receptor Co-Repressor 2 / Q000378:metabolism*; D025941:Protein Interaction Mapping; D011722:Pyrethrins / Q000633:toxicity*; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: D000726:Androgen Antagonists; D007306:Insecticides; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D011722:Pyrethrins; D011944:Receptors, Androgen; C017160:cypermethrin
keywords: Androgen receptor; Anti-androgen; Corepressor; Cypermethrin; Nuclear receptor corepressor; Silencing mediator for thyroid hormone receptors