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

During the preovulatory period, estrogen up-regulates estrogen receptor-alp ha (ER) gene expression in endometrium in female mammals of all species exa mined. The purpose of this study was to determine directly whether estradio l up-regulates ER mRNA by increasing the stability of the message. Endometr ial 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 +/- 1 5%) as well as steady-state concentrations of ER (to 309 +/- 37%), progeste rone receptor (PR; to 165 +/- 19%), and glyceraldehyde 3-phosphate dehydrog enase (GAPDH; to 374 +/- 32%) mRNAs in endometrium, compared to control lev els of 100%. The effects of estradiol on ER mRNA stability in endometrium w ere measured in explants cultured with the transcription inhibitor 5,6-dich loro-1-beta-D-ribofuranosylbenzimidazole, as well as by labeling RNA in viv o 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, a nd c-fos mRNAs were unaffected by treatment. Thus, estradiol up-regulates s teady-state concentrations of ER mRNA in endometrium by a novel posttranscr iptional mechanism.