Anti-androgen effects of the pyrethroid pesticide cypermethrin on interactions of androgen receptor with corepressors. 2013

Chen Pan, and Qi Wang, and Ya-Peng Liu, and Li-Fang Xu, and Yan-Fang Li, and Jin-Xia Hu, and Min Jiang, and Jin-Peng Zhang, and Mei-Rong Zhang, and Hong-Min Yu, and Ji-Long Zhou, and Xiao-Long Zhou, and Li-Chun Xu
School of Public Health, Xuzhou Medical College, Xuzhou, 84 West Huai-hai Road, Xuzhou, Jiangsu 221002, China.

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.

UI MeSH Term Description Entries
D007306 Insecticides Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. Insecticide
D011722 Pyrethrins The active insecticidal constituent of CHRYSANTHEMUM CINERARIIFOLIUM flowers. Pyrethrin I is the pyretholone ester of chrysanthemummonocarboxylic acid and pyrethrin II is the pyretholone ester of chrysanthemumdicarboxylic acid monomethyl ester. Pyrethrin,Pyrethroid,Pyrethroids
D011944 Receptors, Androgen Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA. Androgen Receptors,5 alpha-Dihydrotestosterone Receptor,Androgen Receptor,Dihydrotestosterone Receptors,Receptor, Testosterone,Receptors, Androgens,Receptors, Dihydrotestosterone,Receptors, Stanolone,Stanolone Receptor,Testosterone Receptor,5 alpha Dihydrotestosterone Receptor,Androgens Receptors,Receptor, 5 alpha-Dihydrotestosterone,Receptor, Androgen,Receptor, Stanolone,Stanolone Receptors,alpha-Dihydrotestosterone Receptor, 5
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D000726 Androgen Antagonists Compounds which inhibit or antagonize the biosynthesis or actions of androgens. Androgen Antagonist,Antiandrogen,Antiandrogens,Anti-Androgen Effect,Anti-Androgen Effects,Antiandrogen Effect,Antiandrogen Effects,Antagonist, Androgen,Antagonists, Androgen,Anti Androgen Effect,Anti Androgen Effects,Effect, Anti-Androgen,Effect, Antiandrogen,Effects, Anti-Androgen,Effects, Antiandrogen
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000882 Haplorhini A suborder of PRIMATES consisting of six families: CEBIDAE (some New World monkeys), ATELIDAE (some New World monkeys), CERCOPITHECIDAE (Old World monkeys), HYLOBATIDAE (gibbons and siamangs), CALLITRICHINAE (marmosets and tamarins), and HOMINIDAE (humans and great apes). Anthropoidea,Monkeys,Anthropoids,Monkey
D056971 Nuclear Receptor Co-Repressor 1 A nuclear protein that regulates the expression of genes involved in a diverse array of processes related to metabolism and reproduction. The protein contains three nuclear receptor interaction domains and three repressor domains and is closely-related in structure to NUCLEAR RECEPTOR CO-REPRESSOR 2. Nuclear Factor RIP140,Nuclear Receptor Co-Repressor RIP140,RIP140 Repressor,Receptor Interacting Protein 140,Retinoid X Receptor-Interacting Protein 13,Nuclear Receptor Co Repressor 1,Nuclear Receptor Co Repressor RIP140,Retinoid X Receptor Interacting Protein 13
D056985 Nuclear Receptor Co-Repressor 2 A nuclear co-repressor protein that shows specificity for RETINOIC ACID RECEPTORS and THYROID HORMONE RECEPTORS. The dissociation of this co-repressor from nuclear receptors is generally ligand-dependent, but can also occur by way of its phosphorylation by members of the MAP KINASE SIGNALING SYSTEM. The protein contains two nuclear receptor interaction domains and four repressor domains and is closely-related in structure to NUCLEAR RECEPTOR CO-REPRESSOR 1. SMRT Co-repressor,Silencing Mediator of Retinoic Acid and Thyroid Hormone Receptor,T3 Receptor-associating Factor,TRAC Co-repressor,Co-repressor, SMRT,Co-repressor, TRAC,Nuclear Receptor Co Repressor 2,Receptor-associating Factor, T3,SMRT Co repressor,T3 Receptor associating Factor,TRAC Co repressor
D025941 Protein Interaction Mapping Methods for determining interaction between PROTEINS. Interaction Mapping, Protein,Interaction Mappings, Protein,Mapping, Protein Interaction,Mappings, Protein Interaction,Protein Interaction Mappings

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