Effects of bisphenol A on the expression of cytochrome P450 aromatase (CYP19) in human fetal osteoblastic and granulosa cell-like cell lines.
The effects of bisphenol A (BPA), an endocrine disruptor, on aromatase (CYP19) expression in human osteoblastic (SV-HFO) and ovarian granulosa-like (KGN) cell lines were examined. CYP19 enzyme activity was suppressed in the presence of BPA in a dose-dependent fashion in both cell lines. CYP19 gene transcript expression, as well as activities of promoter I.4 in SV-HFO and promoter II in KGN, was down-regulated by BPA, suggesting that BPA affects CYP19 at the gene-expression level. These data and the previous finding that BPA induced the down-regulation of promoter I.1 activity within the human placental cell line suggest that there may be a conserved signaling pathway that down-regulates CYP19 expression in response to BPA in both cell lines. Additionally, differences between promoter I.4 and II suggest that there may be cell- and promoter-specific down-regulating mechanisms downstream from the actions of BPA.
Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan. masatada@hoshi.ac.jp
Masatada
M
Watanabe
Shuji
S
Ohno
Shizuo
S
Nakajin
D001141:Aromatase / Q000096:biosynthesis*; D001559:Benzhydryl Compounds; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000201:enzymology; D015870:Gene Expression / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology; D010636:Phenols / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098826:Bisphenol A Compounds
D001141:Aromatase; D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds