Dexamethasone attenuates the estradiol-induced increase of IGF-I mRNA in the rat uterus.
In recent years growth factors, e.g. insulin-like growth factor-I (IGF-I), transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF), have been considered as mediators of estradiol-stimulated growth in the uterus. In the liver, dexamethasone (Dex) has been shown to inhibit the IGF-I mRNA increase induced by growth hormone (GH). In the present study the influence of Dex on estradiol-stimulated induction of uterine IGF-I mRNA was examined. The concentration of IGF-I mRNA in the uterus and liver was monitored, as well as the levels of ER mRNA and estrogen receptor (ER). Since it has been previously shown that the maximal induction of uterine IGF-I mRNA after estradiol (E2) stimulation occurs after 21-24 h, Dex was administered to ovariectomized (ovx) rats 3 h before an E2 injection and 24 h before sacrifice. There was a significant decrease in IGF-I mRNA in the Dex+E2 treated rats compared to the rats given E2 only. In both groups an increase was seen compared to the level in the ovx control group. The uterine ER mRNA levels in E2 and Dex+E2 treated animals were significantly elevated compared to the ovx control. There were no significant changes in uterine ER content after hormone treatment compared to the level in ovx control rats. In the liver no effects on IGF-I mRNA were detected. Hepatic ER mRNA was significantly increased in the E2 treated group, compared to both the ovx control group and the animals that received Dex+E2. The hepatic ER level was also increased in the E2 treated group compared to the ovx control and the group which received Dex+E2. In conclusion, Dex does attenuate the estrogen-induced uterine IGF-I mRNA increase in ovx rats. In addition to this, Dex was found to inhibit the estrogen-induced increase in ER and ER mRNA in the liver of ovx rats.
Sahlin
L
L
Department of Woman and Child Health, Karolinska Hospital, Stockholm, Sweden.
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D013006:Growth Hormone / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008099:Liver / Q000187:drug effects; D010052:Ovariectomy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011959:Receptors, Estradiol / Q000037:antagonists & inhibitors / Q000235:genetics; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D004965:Estrogen Antagonists; D005938:Glucocorticoids; D012333:RNA, Messenger; D011959:Receptors, Estradiol; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D013006:Growth Hormone