Pharmacological concentration of resveratrol suppresses aromatase in JEG-3 cells.
Estrogen is crucial in preparing of pregnancy, and its role in the maintenance of pregnancy has yet to be elucidated. During the course of pregnancy, the placenta is responsible for the provision of estrogen. The hormone biosynthesis is catalyzed by cytochrome P450 (CYP) 19 or aromatase. In the present study, we screened several common dietary components and identified the grape polyphenol resveratrol to be a potential inhibitor in the hormone synthesis. In a recombinant protein system resveratrol inhibited the aromatase activity with an IC(50) value of approximately 40 microM. Subsequent analysis was performed in the human placental JEG-3 cells, and 25 microM resveratrol significantly reduced the mRNA abundance in these cells. Since the transcriptional control of CYP19 gene is tissue-specific and the proximal promoter region of exon Ia has previously been shown to be crucial in CYP19 expression in placental cells, we also evaluated the promoter activity of this gene. Reporter gene assays revealed that resveratrol repressed the transcriptional control of promoter Ia. The present study illustrated the possibility that dietary supplementation of resveratrol interfered with the normal functioning of placental cells.
Wang
Yun
Y
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
Leung
Lai K
LK
D001141:Aromatase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000633:toxicity*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004794:Enzyme Repression; D004967:Estrogens / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000633:toxicity*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D047072:Aromatase Inhibitors; D004967:Estrogens; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013267:Stilbenes; D008156:Luciferases; D001141:Aromatase; D000077185:Resveratrol