Abstract
We investigated the effects of natural and synthetic estrogens on estrogen receptor-mediated signal transduction and transcription. To assess estrogen receptor-dependent gene expression, we constructed a reporter plasmid that can express the luciferase gene under the control of the estrogen-responsive element. A transcriptional assay was performed by transfection of the reporter plasmid into estrogen-responsive MCF-7 cells. Transcription was completely dependent on the natural estrogen, 17 beta-estradiol (E2), in a dose-dependent manner. Retinoic acids and other steroid hormones had no effect on gene expression. The effect of synthetic estrogens on estrogen receptor-mediated signal transduction was also examined using the specific reporter assay system. A synthetic estrogen, diethylstilbestrol, exhibited higher activity than E2 at lower concentrations. In addition, transcriptional activities of the (+)- and (-)-enantiomers of indenestrol A, a metabolite of diethylstilbestrol, could be distinguished using the reporter assay system.
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