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Chemosphere. 2016 Sep;158:24-9. doi: 10.1016/j.chemosphere.2016.05.053. Epub 2016 May 27.

Inhibition effect of cypermethrin mediated by co-regulators SRC-1 and SMRT in interleukin-6-induced androgen receptor activation.

Author information

1
School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
2
School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China. Electronic address: lichunxu2002@163.com.

Abstract

It is hypothesized that the pesticide cypermethrin may induce androgen receptor (AR) antagonism via ligand-independent mechanisms. The Real-Time Cell Analysis (RTCA) iCELLigence system was used to investigate the inhibitory effect of cypermethrin on interleukin-6 (IL-6)-induced ligand-independent LNCaP cell growth. Then, the mammalian two-hybrid assays were applied to clarify whether the mechanism of IL-6-induced AR antagonism of cypermethrin was associated with the interactions of the AR and co-activator steroid receptor co-activator-1 (SRC-1) and co-repressor silencing mediator for retinoid and thyroid hormone receptors (SMRT). Cypermethrin inhibited the LNCaP cell growth induced by IL-6. The interactions of AR-SRC-1 and AR-SMRT mediated by IL-6 were suppressed by cypermethrin. The results indicate that the IL-6-mediated AR antagonism induced by cypermethrin is related to repress the recruitment of co-regulators SRC-1 and SMRT to the AR in a ligand-independent manner. Inhibition of the interactions of AR-SRC-1 and AR-SMRT mediated by IL-6 contributes to the AR antagonism induced by cypermethrin.

KEYWORDS:

Androgen receptor; Anti-androgen; Cypermethrin; Interleukin-6; Silencing mediator for retinoid and thyroid hormone receptors; Steroid receptor co-activator-1

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