Evaluation on antagonist activities of polycyclic aromatic hydrocarbons using the yeast two-hybrid detection system...

We constructed an efficient and reliable yeast two-hybrid detection system to evaluate the estrogenic activity of endocrine disruptors (EDs) (Lee et al., Journal of Biochemistry, 131, 2002). This system employs the interaction between the human estrogen receptor beta (hERbeta) ligand binding domain and the co-activator SRC1. The extent of transcriptional activation by those chemicals correlated with estrogenic activities as measured by other assay systems. We applied this assay system to evaluate anti-estrogenic activities and found that known antagonistic compounds, 4-hydroxytamoxifen (OHT) and ICI 182,780, effectively inhibited reporter gene induction by 17beta-estradiol. We then tested the estrogenic and anti-estrogenic activities of polycyclic aromatic hydrocarbons (PAHs) using this assay system. PAHs only weakly induced the lacZ reporter gene at higher concentrations, but clearly showed an inhibitory effect on reporter gene induction by 10(-9) M 17beta-estradiol. These results suggest that PAHs are potentially anti-estrogenic and that the employed yeast detection system could be applicable to primary screening for effectors on estrogen receptor functions.