Evaluation on antagonist activities of polycyclic aromatic hydrocarbons using the yeast two-hybrid detection system for endocrine disruptors.
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.
Lee
Haeng-Seog
HS
Department of Marine Biotechnology, Anyang University, Incheon 417-833, South Korea. haengseog@anyang.ac.kr
Cho
Eun-Min
EM
Jung
Jae Hak
JH
Ohta
Akinori
A
D052244:Endocrine Disruptors / Q000378:metabolism / Q000494:pharmacology*; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007723:Korea; D011084:Polycyclic Aromatic Hydrocarbons / Q000494:pharmacology*; D020798:Two-Hybrid System Techniques; D014871:Water Microbiology
D052244:Endocrine Disruptors; D047629:Estrogen Receptor beta; D011084:Polycyclic Aromatic Hydrocarbons