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-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 microg 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 >/= 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.
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Department of Animal Science and Center for Animal Biotechnology, TexasA&M University, College Station 77843-2471, USA. ning@cvm.tamu.edu
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D000818:Animals; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D004355:Drug Stability; D004717:Endometrium / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006207:Half-Life; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics; D012756:Sheep / Q000378:metabolism*; D013891:Thiouridine; D014599:Uterus / Q000033:anatomy & histology
D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013891:Thiouridine; D004958:Estradiol; D004004:Dichlororibofuranosylbenzimidazole; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases