Insulin-like growth factor-I stimulates proliferation of mouse uterine epithelial cells in primary culture

Estrogens stimulate proliferation and differentiation of uterine epithelial cells in vivo. Mitogenic action of estrogens may be mediated by growth factors such as insulin-like growth factor-I (IGF-I). This study was designed to determine whether IGF-I and insulin affect proliferation of uterine epithelial cells obtained from 3- to 4-week-old immature female mice in a serum-free culture system. The epithelial cell number on Day 5 in culture was significantly increased by adding IGF-I (10 and 100 ng/ml) or insulin (100 and 1000 ng/ml) to the culture media, indicating that IGF-I is more effective than insulin in inducing the epithelial growth. The epithelial DNA synthesis was significantly stimulated by IGF-I (1 and 10 ng/ml), suggesting that both the epithelial proliferation and their detachment from substratum are stimulated by 1 ng/ml of IGF-I, but that the former is more accelerated than the latter by 10 ng/ml of IGF-I. These results demonstrate that both IGF-I and insulin directly stimulate the growth of uterine epithelial cells, and suggest that insulin may act via IGF-I receptors. IGF- I immunoreactivity was detected in the cytoplasm of the cultured cells, indicating that the cells synthesize IGF-I. Estradiol-17β (E₂) at lower concentrations (0.001-0.1 nM) tended to increase the number of epithelial cells, while E₂ at higher concentrations (1 to 100 nM) did not affect it. It is highly probable that IGF-I produced in endometrial cells induces their proliferation by an autocrine or paracrine mechanism.