Insulin-like Growth Factor-I Effects on ADP-Ribosylation Processes and Interactions with Glucocorticoids During Maturation and Differentiation of Astroglial Cells in Primary Culture

Abstract

Nervous system function depends upon the extensive and intimate coupling between neuronal cells and glial cells [1, 2]. We have recently shown [3, 4] that during differentiation in vitro, astroglial cells in primary culture release polypeptide growth factors that exert dramatic effects on the differentiation of an immortalized hypothalamic LH-RH neuronal (Gt1-1 subclone) cell line [3–6]. The growth factors (GFs) have emerged as crucial intercellular signaling agents that coordinate the developmental and adult physiological processes of both astrocytes and neurons [6–8]. Insulin-like growth factors I and II (IGF-I and IGF-II) are peptide growth factors structurally related to insulin. IGF-I, IGF-II and fibroblast growth factors (FGFs) are synthesized by developing astroglial cells and exert autocrine and paracrine mitogenic actions [6–9]. Primary astroglial cells possess IGF receptors and synthesize IGFs and IGF binding proteins [9,10]. Epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), IGF-I and insulin are potent mitogens capable of inducing cell division in various cell types and in particular in cultured cells from the central nervous system (CNS) [6–8, 11–13]. The effects of bFGF on the morphology of cultured astrocytes prepared from various areas of newborn rat brain, and on their expression of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) have also been described [14]. Furthermore, EGF acts as a neurotrophic agent preferential for dopaminergic neurons in rat embryonic mesencephalic cultures [12], and enhances the proliferation of cultured astrocytes from rat brain [7,15].