Effects of cypermethrin on the ligand-independent interaction between androgen receptor and steroid receptor coactivator-1.
The pyrethroid insecticide, cypermethrin has been considered as an environmental anti-androgen by interfering with the androgen receptor (AR) transactivation. In order to clarify the effects of cypermethrin on the ligand-independent interaction between the AR and SRC-1, the mammalian two-hybrid assay has been developed in the study. The AR N-terminal domain 1-660 amino acid residues were subcloned into the plasmid pVP16 to construct the vector pVP16-ARNTD. The SRC-1 C-terminal domain 989-1240 amino acid residues were subcloned into the plasmid pM to construct the vector pM-SRC-1. The fusion vectors pVP16-ARNTD, pM-SRC-1 and the pG5CAT Reporter Vector were cotransfected into the CV-1 cells. The AR AF1 interacted with SRC-1 in the absence of exogenous ligand 5α-dihydrotestosterone (DHT). Furthermore, DHT did not enhance the interaction between AR AF-1 and SRC-1 at the concentrations from 10(-10)M to 10(-8)M. Cypermethrin inhibited the interaction between the AR AF1 and SRC-1, and the significant reduction was detected at the concentration of 10(-5)M. It is suggested that the interaction between the AR AF1 and SRC-1 is ligand-independent. Cypermethrin inhibits AR activity by disrupting the ligand-independent AR-SRC-1 interaction.
School of Public Health, Xuzhou Medical College, Xuzhou, 84 West Huai-hai Road, Xuzhou, Jiangsu 221002, China.
Chen
C
Pan
Ya-Peng
YP
Liu
Yan-Fang
YF
Li
Jin-Xia
JX
Hu
Jin-Peng
JP
Zhang
Hong-Mei
HM
Wang
Jing
J
Li
Li-Chun
LC
Xu
D002460:Cell Line; D006801:Humans; D007248:Infertility, Male / Q000139:chemically induced* / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D056920:Nuclear Receptor Coactivator 1 / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011722:Pyrethrins / Q000633:toxicity*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques
C410798:AR protein, human; D007306:Insecticides; D011722:Pyrethrins; D011944:Receptors, Androgen; C017160:cypermethrin; D056920:Nuclear Receptor Coactivator 1