Estrogen receptor-mediated transcriptional activation by 17 beta-estradiol and its analogs.
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.
Oda
T
T
Kyoritsu College of Pharmacy, Tokyo, Japan.
Tsuchiya
T
T
Sato
Y
Y
Yasukochi
Y
Y
D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D011960:Receptors, Estrogen / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D011960:Receptors, Estrogen; D004958:Estradiol; D004054:Diethylstilbestrol