Estradiol up-regulates estrogen receptor-α messenger ribonucleic acid in sheep endometrium by increasing its stability

During the preovulatory period, estrogen up-regulates estrogen receptor-alpha (ER) gene expression in endometrium in female mammals of all species examined. The purpose of this study was to determine directly whether estradiol up-regulates ER mRNA by increasing the stability of the message. Endometrial tissue was collected from ovariectomized ewes 18 h after the ewes were injected with 50 mu g estradiol. Previous work indicated rapid accumulation of ER mRNA at this time. Estradiol increased uterine weights (to 157 +/- 15%) as well as steady-state concentrations of ER (to 309 +/- 37%), progesterone receptor (PR; to 165 +/- 19%), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH; to 374 +/- 32%) mRNAs in endometrium, compared to control levels of 100%. The effects of estradiol on ER mRNA stability in endometrium were measured in explants cultured with the transcription inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, as well as by labeling RNA in vivo with 4-thiouridine. Both assays indicated that estradiol enhanced ER mRNA stability (half-life increased from 9 h to greater than or equal to 24 h). The estradiol effect was specific, because the stabilities of PR, GAPDH, and c-fos mRNAs were unaffected by treatment. Thus, estradiol up-regulates steady-state concentrations of ER mRNA in endometrium by a novel posttranscriptional mechanism.