Bisphenol A downregulates CYP19 transcription in JEG-3 cells.
Bisphenol A is an industrial contaminant and is considered to be an endocrine disruptor; its estrogenic property has been reported in many studies. Because of its ubiquitous existence in our environment, bisphenol A has drawn much discussion on its safety issues. Estrogen is important in the maintenance of human pregnancy, and the placenta is the major site of synthesis during this period of time. Aromatase or CYP19 catalyses the conversion of estrogen from its precursor, and is highly expressed in placental cells. In the present study, we examined the ability of the toxicant in suppressing the transcription of CYP19 in JEG-3 cells. Cells treated with bisphenol A displayed a reduced aromatase activity. Real-time PCR analysis indicated that 5muM of the compound significantly reduced the mRNA expression in these cells. As the transcriptional activity of CYP19 gene is controlled by the proximal promoter region of exon I.1 in placental cells, the promoter activity of this gene fragment and exon-I.1-spliced mRNA abundance were also evaluated. Both results indicated that bisphenol A repressed the transcriptional control of promoter I.1. The present study showed that bisphenol A potentially reduced estrogen synthesis by downregulating CYP of placental cells. This information could be useful for evaluating the exposure limit of bisphenol A.
Huang
Hui
H
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Leung
Lai K
LK
D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D001559:Benzhydryl Compounds; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D005091:Exons / Q000235:genetics; D005260:Female; D005506:Food Contamination; D006801:Humans; D008156:Luciferases / Q000235:genetics; D010636:Phenols / Q000633:toxicity*; D010920:Placenta / Q000166:cytology / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098826:Bisphenol A Compounds
D001141:Aromatase; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D008156:Luciferases; D010636:Phenols; D012333:RNA, Messenger; D011994:Recombinant Proteins; C006780:bisphenol A; D000098826:Bisphenol A Compounds