INSULIN-LIKE GROWTH FACTOR-I (IGF-I) PRODUCTION BY ASTROGLIAL CELLS - REGULATION AND IMPORTANCE FOR EPIDERMAL GROWTH FACTOR-INDUCED CELL REPLICATION

The insulin-like growth factors are postulated to play a role during brain development. Because they are believed to act in a paracrine/autocrine manner, the production of insulin-like growth factor-I (IGF-I) by cultured astroglial cells was examined. Quantities of IGF-I in conditioned media were determined by RIA after separation of IGFs from IGF-binding proteins by high-pressure liquid chromatography. Astrocytes from 1-day-old rats and the rat glioma cell line (C6) both secreted 7.5-kDa IGF-I. A peak of immunoreactivity with an apparent mol wt of 12,000 was additionally present in media conditioned by C6 cells. Exposure to epidermal growth factor (EGF) increased media content of immunoreactive IGF-I slightly (60%) in C6 cells but more than 2-fold in normal astrocytes. Fibroblast growth factor also increased the amount of IGF-I contained in media conditioned by normal astrocytes. To determine whether the secreted IGF-I was biologically active, media IGFs were immunoneutralized with a monoclonal antibody (Sm 1.25). In the presence of the antibody, EGF-stimulated astrocyte replication was blocked. These data indicate that IGF-I secretion by rodent astrocytes is stimulated by factors thought to be important for brain growth and development and that the IGFs are likely intimate participants in EGF-induced astrocyte growth.