Inhibitory Effects of Cypermethrin on Interactions of the Androgen Receptor with Coactivators ARA70 and ARA55

Abstract

Objective: The purpose of this study was to investigate the anti-androgenic mechanism of cypermethrin involving coactivators.

Methods: Mammalian two-hybrid assays were performed to study the effects of cypermethrin on interactions of the androgen receptor (AR) with the coactivators androgen receptor-associated protein 70 (ARA70) and androgen receptor-associated protein 55 (ARA55).

Results: The results showed that AR-ARA70 and AR-ARA55 interactions were remarkably enhanced by dihydrotestosterone (DHT, P ≤ 0.05). Cypermethrin inhibited DHT-induced AR-ARA70 and AR-ARA55 interactions significantly ( P ≤ 0.05).

Conclusion: The study indicates that cypermethrin exhibits inhibitory effects on AR transcription associated with repression of AR-ARA70 and AR-ARA55 interactions in a ligand-dependent manner. The data show novel anti-androgenic mechanisms of cypermethrin that contribute to male reproductive toxicology.

Keywords: Androgen receptor signaling; Androgen receptor-associated protein 55; Androgen receptor-associated protein 70; Cypermethrin.