Influence of blockers for the estrogen receptor (ER) and type 1 IGF-receptor on the levels of ER, ER mRNA and IGF-I mRNA in the rat uterus.
The effects on the uterine concentration of the estrogen receptor (ER), ER mRNA and IGF-I mRNA were monitored in ovariectomized (OVX) rats treated with blockers for the estrogen receptor (ER) (ICI 182780) or the type 1 IGF receptor (H-1356), alone or in combination with estradiol (E2). The hormone-mediated increase in uterine wet weight after E2 treatment was prevented by a simultaneous injection of ICI 182780. The levels of IGF-I mRNA and ER mRNA increased in rats given estradiol (E2), but not in those also receiving ICI 182780. The level of uterine ER was decreased in all animals that received ICI 182780. H-1356 (H) given as a continuous infusion decreased the estradiol-induced increase in uterine wet weight 24 h after a single E2 injection, but not 48 h after the first (of two) E2 injections. The IGF-I mRNA was increased in the E2 treated group after 24 h, and in both the E2 and H + E2 treated groups after 48 h. The ER mRNA was increased in the E2 treated group after 24 h, but not after 48 h. When H-1356 was given as two single injections and estradiol was or was not administered together with the second injection, the uterine wet weight was not increased as in the group receiving E2 only. The levels of IGF-I mRNA as well as ER mRNA were increased both after E2 and H + E2 treatment. In conclusion, the uterine growth stimulated by E2 was prevented by simultaneous treatment with ICI 182780. In addition a type 1 IGF-receptor blocker, which is an IGF-I analogue inhibiting the autophosphorylation of the receptor, also prevented the hormone-induced uterine growth after 24 h, but not after 48 h, when given as a continuous infusion. The results imply that the growth process stimulated by estradiol utilizes the ER receptor, and also the type 1 IGF-receptor during the first 24 h after E2 treatment.
Division for Reproductive Endocrinology, Department of Woman and Child Health, Karolinska Hospital Stockholm, Sweden.
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Sahlin
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Eriksson
D000818:Animals; D003600:Cytosol / Q000737:chemistry; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000031:analogs & derivatives / Q000235:genetics*; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D011960:Receptors, Estrogen / Q000032:analysis* / Q000235:genetics; D014599:Uterus / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development
D004965:Estrogen Antagonists; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1