Differential Interactions with Estrogen Receptor a of Bisphenol A and ( ERa ) and ER / 3 173 - estradiol

Bisphenol A (BPA), a monomer of plastic used in consumer products, is abundant in the environment and enters the body by ingestion or adsorption. We developed a cell based transcription assay system using a reporter gene under the transcriptional control of estrogen receptor a (ERa) as well as ER~3 and performed chloramphenicol acetyltransferase (CAT) assay on HeLa cells transfected with either human ERa cDNA or ER/I cDNA to characterize the estrogenic effect of BPA. Estrogenic activity of BPA was detectable at a concentration of 10-9 M and the activity increased in a dose dependent manner between concentrations of 10_9 M and 10-6 M of BPA for both ERa and ER. The estrogenic activity of 17 j3-estradiol at a concentration of 10-g M was almost compatible with that of BPA at the concentration of 10-6 M of BPA for ERa as well as ER. CAT activity was significantly decreased when cells expressing ERa were incubated with 10-6 M of BPA and 10-8 M of 17j3-estradiol while the activity was essentially the same for ER~3 in the same condition, indicating that BPA exhibits only agonistic action for ERJ3 whereas it has dual actions as an agonist and antagonist of estrogen for ERa. These results indicates that BPA exerts its effects in ER subtype specific way, thus suggesting that the mode of action of endocrine disruptors are more complex than thought.