title: ICI 182,780 acts as a partial agonist and antagonist of estradiol effects in specific cells of the sheep uterus.
abstract: We assessed the ability of ICI 182,780 (ICI) to block the estradiol (E2) responses of genes within the sheep uterus. Ovariectomized ewes in the 'ICI+E2' treatment group received a uterine infusion with 10(-7) M ICI for 14 h, an injection of 50 microg E2 6 h after the infusion started, and were hysterectomized 18 h postinjection. Other groups received only ICI or E2, or neither treatment ('Con'). Both E2 and ICI increased the wet weight of dissected endometrium: averaging 10.0+/-1.2 g for ICI+E2, ICI, and E2 groups compared to 6.8+/-0.6 g for Con. Slot blot analyses of endometrial RNA showed that estrogen receptor-alpha (ER), progesterone receptor (PR), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), cyclophilin, actin and c-fos mRNAs responded to E2 treatment: the first five increased an average of 60% while the last decreased 38%. In situ hybridization identified more subtle ICI effects: agonistic up-regulation of GAPDH mRNA in superficial endometrial cells, and antagonistic down-regulation of ER and PR mRNAs in the inner layer of the myometrium. Thus, we conclude that the agonist versus antagonist effects of ICI relative to those of E2 are a function of the gene examined as well as the specific cell within the uterus.
authors.affiliation: Department of Animal Science, Texas A&M University, College Station, TX 77843-2471, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Robertson
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: N H
authors.initials: NH
authors.lastname: Ing
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004717:Endometrium / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000819:agonists* / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects; D017403:In Situ Hybridization; D012756:Sheep; D014599:Uterus / Q000166:cytology / Q000187:drug effects*
chemical_list: D004965:Estrogen Antagonists; D000077267:Fulvestrant; D004958:Estradiol