Localization of the Sites of Synthesis and Action of Insulin-Like Growth Factor-I in the Rat Uterus

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Abstract
In this report we have used in situ hybridization to localize insulin-like growth factor-l (IGF-l) expression in the uterus and have examined the effects of exogenous IFG on 3H-methyl thymidine incorporation into DNA, in uterine sections in organ culture. IGF-l mRNA was detected in all layers of the uterus but was particularly abundant in the outer longitudinal smooth muscle layer. Although IGF-I mRNA was detectable in untreated, immature rat uteri, the abundance in each layer of the uterus was increased after 17.beta.-estradiol (E2) administration. A similar increase was seen in uteri from ovariectomized, hypophysectomized rats treated with E2. IGF-l when added to uterine sections in organ culture had no significant effect on DNA synthesis in the absence of E2. However, a dose-dependent increase in DNA synthesis was seen in the presence of E2. The half-maximal and maximal responses required 1 and 10 ng IGF-l, respectively. Autoradiographic localization of 3H-methyl thymidine incorporation into DNA demonstrated that the majority of the DNA synthesis occurred in the stromal layer. These findings are consistent with the hypothesis that IGF-I may function as a paracrine growth factor, mediating stromal-myometrial cell interaction.