Rat C6 glial cells synthesize insulin-like growth factor I (IGF-I) and express IGF-I receptors and IGF-II/mannose 6-phosphate receptors

• Published in: Endocrinology (Philadelphia) Vol. 124; no. 4; p. 1727
• Main Authors: Kiess, W, Lee, L, Graham, D E, Greenstein, L, Tseng, L Y, Rechler, M M, Nissley, S P
• Format: Journal Article
• Language: English
• Published: United States 01-04-1989
• Subjects: Animals; Blotting, Northern; Cell Membrane - analysis; Cell Membrane - ultrastructure; Cells, Cultured; DNA - biosynthesis; Gene Expression Regulation; Insulin-Like Growth Factor I - biosynthesis; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - secretion; Neuroglia - cytology; Neuroglia - metabolism; Neuroglia - ultrastructure; Rats; Receptor, IGF Type 2; Receptors, Cell Surface - analysis; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Somatomedin; RNA, Messenger - metabolism; Somatomedins - biosynthesis
• ISSN: 0013-7227
• DOI: 10.1210/endo-124-4-1727

We have used the rat C6 glial cell line as a model system to study the role of insulin-like growth factors (IGF) in neuroglial cells of the central nervous system (CNS). Northern blot analysis of C6 RNA demonstrated the presence of IGF-I mRNA and undetectable IGF-II mRNA. IGF-I and IGF-binding protein(s), but not IGF-II, were detected in C6 glial cell-conditioned medium. The level of IGF-I was 1-4 ng/ml in conditioned medium based on a human IGF-I standard. The immunoreactive IGF-I inhibited [125I]IGF-I binding to the IGF-I receptor on chick embryo fibroblasts and stimulated [3H]thymidine incorporation into chick embryo fibroblast DNA. Competitive binding and affinity cross-linking experiments using [125]IGF-I and [125I]IGF-II demonstrated the presence of IGF-I receptors (type I) and IGF-II/mannose 6-phosphate receptors (type II) on C6 glial cell membranes. An immunoglobulin (no. 3637) directed against the rat IGF-II receptor blocked the degradation of [125I]IGF-II added to C6 glial cells, presumably by blocking receptor-mediated internalization. We were unable to demonstrate an autocrine role for IGF in the C6 glial cell line, since [3H]thymidine incorporation into DNA was stimulated equally well by IGF-I-deficient rat serum and normal serum, and added IGF did not stimulate [3H]thymidine incorporation into DNA when tested alone or when added to IGF-I-deficient serum. We propose that neuroglial cell-derived IGF-I may serve as a paracrine growth stimulus in the central nervous system.