| Estrogens and corticotrophin-releasing hormone (CRR) produced by the placenta are important in the maintenance of pregnancy and control of parturition in human. Human placenta is the primary source of estrogen after the ninth week of gestation. Aromatase or CYP19 is the enzyme which is primarily responsible for catalyzing the conversion of estrogen from its precursor in the placental cells. The overall objective of this study was to investigate the effect of bisphenol-A and genistein on the expression of genes responsible for the synthesis of estrogen and corticotrophin-releasing hormone.;Bisphenol-A is an industrial contaminant whose estrogenic property has been reported in many studies. Because of its ubiquitous existence in our environment, the safety of bisphenol-A has been drawn much attention. By employing real-time PCR, bisphenol-A was shown to down-regulate aromatase and up-regulate CRR transcription in JEG-3 cells. The promoter activities of the two genes were evaluated by employing electromobility shift assays and gene reporter assays. The results were consistent with the mRNA expression. Furthermore, we demonstrated that bisphenol-A could affect the estrogen metabolism and CRR expression in mice. These data are indeed useful for illustrating bisphenol-A's toxicological properties.;Genistein is a phytoestrogen isolated from soyabeans. Given the differential interactions with different estrogen receptor isoforms, genistein is generally considered to be a selective estrogen receptor modulator (SERM). While Genistein is commercially available as nutraceutical for women; however, the potential safety issues have not been fully addressed. In the trophoblast cells SGHPL, exon II (90%) was the overwhelming promoter used with trace levels of usage from promoter I.3, 1.4 and I.l. Real-time PCR indicated that genistein down-regulated aromatase through promoter II. CRE-driven CRH transactivity appeared to be compromised upon genistein treatment. Western blot analysis II also signified MAPK activation in these placental cells. An in vivo study also demonstrated that genistein could affect normal parturition in LPS-sensitized mice. This information may provide some scientific basis for establishing the safety level of genistein intake during pregnancy. |
