Estrogen regulation of the estrogen receptor and insulinlike growth factor-I in the rat uterus: a potential coupling between effects of estrogen and IGF-I

Abstract

The interrelationship between estrogen and insulinlike growth factor-I (IGF-I) in the regulation of uterine growth was studied in the rat. The levels of the estrogen receptor (ER), ER mRNA, and IGF-I mRNA in rat uterus and liver monitored. Uterine ER in normal cycling rats highest in proestrus and diestrus, as was IGF-I mRNA. ER and mRNA and plasma estradiol peaked in proestrus. Hepatic ER and mRNA and IGE-I mRNA were highest in diestrus, whereas ER was not significantly changed suring the estrous cycle. The temporal effects of multiple infections or continuous infusion of 17 β-estradiol in ovariectomized rats were examined. In the uterus of animals subjected to multiple injections, a 10-fold increase in IGF-I mRNA was seen 24 h after the start of the treatment, whereas rats given continuous infusion estradiol showed a more than 16-fold increase. In both groups, the inrease of IGF-I mRNA was transient although estrogen treatment was continued. To study local hormonal effects, ovariectomized rats were given estradiol in vaginal implants. The uterine IGF-I mRNA level increased two-fold in 3 days. The ER and mRNA level increased 1.5-fold and the uterine weights were doubled. The plasma estradio concentration did not change during the treatment. A separate experiment was carried out to establish whether IGF-I itself exercises estrogenlike effects.Ovariectomized rats were given hrIGF-I in osmotic minipumps for 3 days. The uteri of the treated animals weighed significantly more than did the controls. Quantitation of the level of uterine estrogen receptors revealed a significant decrease. In conclusion, estrogen appears to be an important regulator of IGF-I mRNA since an increase in IGF-I mRNA covaries with estrogen during the estrous cycle. In ovariectomized rats, systematic administration of estrogen transiently increased IGF-I mRNA. Administration of IGF-I can cause estrogenic effects on the uterus in terms of increased weight. IGF-I down-regulated the uterine estrogen receptor, which suggests a reciprocal dependence between estrogen and IGF-I in the effects on the uterus.