ICI 182,780 acts as a partial agonist and antagonist of estradiol effects in specific cells of the sheep uterus.
Overview
Research
Identity
Additional Document Info
Other
View All
Overview
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.