Estrogenicity of bisphenol A in a human endometrial carcinoma cell line.
The ability of bisphenol A (BPA) to affect human estrogen receptor (ER) binding, expression of progesterone receptor (PR) mRNA and protein, and cell proliferation has been measured in the human endometrial cell line, ECC-1. Although less potent than 17beta-estradiol, BPA was able to bind to the human uterine ER. BPA also induced both mRNA and protein to levels similar to E2. BPA-mediated PR mRNA induction was antagonized by ICI, suggesting an ER-mediated pathway. Finally, E2 produced a 2-fold increase in cell number, while BPA showed no difference compared with vehicle control. The increase by E2 was inhibited by treatment with the either ICI 182,780 (ICI) or BPA, suggesting similar binding sites. Although ER binding is similar, E2 affected both proliferation and PR expression, while BPA only affected PR gene expression. The results of this study provide evidence that two ER agonists can act differentially in vitro to affect the expression of genes involved in regulating cellular growth and development, though the human risk potential remains to be determined.
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.
R M
RM
Bergeron
T B
TB
Thompson
L S
LS
Leonard
L
L
Pluta
K W
KW
Gaido
D001559:Benzhydryl Compounds; D001667:Binding, Competitive; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010636:Phenols / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004958:Estradiol; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C006780:bisphenol A; D000098826:Bisphenol A Compounds