Tamoxifen up-regulates oestrogen receptor-alpha, c-fos and glyceraldehyde 3-phosphate-dehydrogenase mRNAs in ovine endometrium.
Tamoxifen, the antiestrogen most widely used in medicine, was tested in ewes to determine whether it antagonizes oestradiol up-regulation of ER, PR, and other genes reported to be oestrogen-modulated (c-fos, oxytocin receptor (OTR), glyceraldehyde phosphate dehydrogenase (GAPDH), and apolipoprotein AI (apo AI)) in endometrium and liver. Ovariectomized ewes (n = 6 ewes per group) were injected with 20 mg tamoxifen (Tam) 24 h prior to tissue collection, 50 microg oestradiol (E2) 18 h prior to tissue collection, both drugs (T + E2) or drug vehicle (Con). E2 treatment resulted in 857 +/- 93 pg oestradiol/g endometrium. Gross uterine characteristics of Tam- and T + E2-treated ewes were intermediate to those in Con and E2 groups. In endometrium, Tam treatment mimicked E2 treatment in up-regulating ER, c-fos, and GAPDH mRNAs two- or three-fold. However, neither E2 nor Tam treatments affected concentrations of OTR mRNA in endometrium, or ER, c-fos, GAPDH, OTR and apo AI mRNAs in liver. Like oestradiol, tamoxifen stabilized endometrial ER mRNA more than 3-fold in endometrial explants cultured with the transcription inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). Thus, tamoxifen acts as an oestradiol agonist in ovine endometrium and shares a posttranscriptional mechanism with oestradiol in the up-regulation of ER gene expression.
Robertson
J A
JA
Department of Animal Science, Institute of Biosciences and Technology, Texas A&M University, College Station 77843-2471, USA.
Bhattacharyya
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S
Ing
N H
NH
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics; D001483:Base Sequence; D015152:Blotting, Northern; D017931:DNA Primers; D018076:DNA, Complementary; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics*; D018045:Receptors, Oxytocin / Q000235:genetics; D012756:Sheep; D013629:Tamoxifen / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
D016632:Apolipoprotein A-I; D017931:DNA Primers; D018076:DNA, Complementary; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D018045:Receptors, Oxytocin; D013629:Tamoxifen; D004958:Estradiol; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases