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 ewe s to determine whether it antagonizes oestradiol up-regulation of ER, PR, a nd other genes reported to be oestrogen-modulated (c-fos, oxytocin receptor (OTR), glyceraldehyde phosphate dehydrogenase (GAPDH), and apolipoprotein Al (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 collec tion, 50 mu g oestradiol (E2) 18 h prior to tissue collection, both drugs ( T + E2) or drug vehicle (Con). E2 treatment resulted in 857 +/- 93 pg oestr adiol/g endometrium. Gross uterine characteristics of Tam- and T + E2-treat ed ewes were intermediate to those in Con and E2 groups. In endometrium, Ta m treatment mimicked E2 treatment in up-regulating ER, c-fos, and GAPDH mRN As two- or three-fold. However, neither E2 nor Tam treatments affected conc entrations of OTR mRNA in endometrium, or ER, c-fos, GAPDH, OTR and apo AI mRNAs in liver. Like oestradiol, tamoxifen stabilized endometrial ER mRNA m ore than 3-fold in endometrial explants cultured with the transcription inh ibitor 5,6-dichloro- 1-beta-D-ribofuranosylbenzimidazole (DRB). Thus, tamox ifen acts as an oestradiol agonist in ovine endometrium and shares a posttr anscriptional mechanism with oestradiol in the up-regulation of ER gene exp ression. (C) 1998 Elsevier Science Ltd. All rights reserved.