ESTROGEN REGULATION OF THE ESTROGEN-RECEPTOR AND INSULIN-LIKE GROWTH-FACTOR-I IN THE RAT UTERUS - A POTENTIAL COUPLING BETWEEN EFFECTS OF ESTROGEN AND IGF-I

The interrelationship between estrogen and insulinlike growth factor-I (IGF-I) in the regulation of uterine growth was studied in the rat. T he levels of the estrogen receptor (ER), ER mRNA, and IGF-I mRNA in ra t uterus and liver were monitored Uterine ER in normal cycling rats wa s highest in proestrus and diestrus, as was IGF-I mRNA. ER mRNA and pl asma estradiol peaked in proestrus. Hepatic ER mRNA and IGF-I mRNA wer e highest in diestrus, whereas ER was not significantly changed during the estrous cycle. The temporal effects of multiple injections or con tinuous infusion of 17 beta-estradiol in ovariectomized rats were exam ined In the uterus of animals subjected to multiple injections, a 10-f old increase in IGF-I mRNA was seen 24 h after the start of the treatm ent, whereas rats given continuous infusion of estradiol showed a more than 16-fold increase. In both groups, the increase of IGF-I mRNA was transient although estrogen treatment was continued. To study local h ormonal effects, ovariecromized rats were given estradiol in vaginal i mplants. The uterine IGF-I mRNA level increased two-fold in 3 days. Th e ER mRNA level increased 1.5-fold and the uterine weights were double d The plasma estradiol concentration did not change during the treatme nt. A separate experiment was carried out to establish whether IGF-I i tself exercises estrogenlike effects. Ovariectomized rats were given h r IGF-T in osmotic minipumps for 3 days. The uteri of the treated anim als weighed significantly more than did the controls. Quantitation of the level of uterine estrogen receptors revealed a significant dea eas e. 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, systemic 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 r eciprocal dependence between estrogen and IGF-I in the effects on the uterus.