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ToxSci Advance Access published online on June 12, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg150
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received January 29, 2003; accepted May 5, 2003
© 2003 Society of Toxicology

Endocrine Toxicology

Anti-Androgenic Effects of Bisphenol A and Nonylphenol on the Function of Androgen Receptor

Hyun Ju Lee 1, Soma Chattopadhyay 1, Eun-Yeung Gong 1, Ryun Sup Ahn 1, and Keesook Lee 1*

1 Hormone Research Center, Chonnam National University, Gwangju 500-757, Rep. of Korea

* To whom correspondence should be addressed. E-mail: klee{at}chonnam.ac.kr.


  Abstract

By using a yeast detection system for androgenic and anti-androgenic effects of chemicals, we identified bisphenol A (BPA) and nonylphenol (NP) as anti-androgens. In this study, we report molecular mechanisms for the anti-androgenic action of BPA and NP. In ARhLBD-ASC1 yeast two-hybrid system which reflects the androgen-dependent interaction between androgen receptor (AR) and its coactivators, Activating Signal Cointegrator 1 (ASC1), BPA and NP acted as potent AR antagonists comparable to a known strong antagonist, cyproterone acetate. Ligand competition assays revealed that [3H]5{alpha}-DHT binding to AR is inhibited maximum 30 and 40% at approximately 5 nM of NP and 50 nM of BPA, respectively. In addition, the nuclear translocation of GFP-AR fusion protein in the presence of testosterone was affected by addition of BPA and NP, which cause rather dispersed distribution of GFP-AR between the nuclear and the cytoplasmic compartment. Furthermore, in transient transfection assays, androgen-induced AR transcriptional activity was inhibited by BPA and NP. Taken together, the results suggest that BPA and NP affect multiple steps of the activation and function of AR, thereby inhibiting the binding of native androgens to AR, AR nuclear localization, AR interaction with its coregulator and its subsequent transactivation. These data may help us better understand the biological alterations induced by these environmental compounds.

Key Words: bisphenol A, nonylphenol, AR, androgen, anti-androgen, endocrine disruptor .


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