Estrogen Receptor (cid:1) (ER (cid:1) ) Mediates Stimulatory Effects of Estrogen on Aromatase ( CYP19 ) Gene Expression in Human Placenta

A 246-bp region upstream of placenta-specific exon I.1 of the human aromatase ( hCYP19 ) gene mediates placenta-specific, developmental, and O 2 regulation of expression. In this study, trophoblast differentiation and associated induction of CYP19 expression were prevented when cytotrophoblasts were cultured in phenol red-free medium containing charcoal-stripped serum or with the estrogen receptor (ER) antagonist, ICI 182,780, suggesting a stimulatory role of estrogen/ER. ER (cid:1) protein was expressed in human trophoblasts and increased during syncytiotrophoblast differentiation, whereas ER (cid:2) was undetectable. Mutational analysis revealed that an estrogen response element-like sequence (ERE-LS) at (cid:1) 208 bp is required for inductive effects of estradiol/ER (cid:1) on hCYP19I.1 promoter activity in transfected COS-7 cells. Increased binding of syncytiotrophoblast compared with cytotrophoblast nuclear proteins to the ERE-LS was observed in vitro ; how-ever, ER (cid:1) antibodies failed to supershift the complex and in vitro -transcribed/translated ER (cid:1) did not bind. Nonetheless, chromatin immunoprecipitation assays in cultured trophoblasts revealed recruitment of endogenous ER (cid:1)

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