title: Insulin-like growth factor-I stimulates proliferation of mouse uterine epithelial cells in primary culture.
abstract: 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-17 beta (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.
authors.affiliation: Department of Biology, Faculty of Science, Okayama University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shiraga
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Miyake
authors.forename: S
authors.initials: S
authors.lastname: Takeuchi
authors.forename: H
authors.initials: H
authors.lastname: Fukamachi
mesh_terms: D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007633:Keratins / Q000378:metabolism; D051379:Mice; D014599:Uterus / Q000166:cytology* / Q000187:drug effects
chemical_list: D007328:Insulin; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007633:Keratins