DIFFERENTIAL-EFFECTS OF BASIC FIBROBLAST GROWTH-FACTOR, EPIDERMAL GROWTH-FACTOR, TRANSFORMING GROWTH-FACTOR-ALPHA, AND INSULIN-LIKE GROWTH-FACTOR-I ON A HYPOTHALAMIC GONADOTROPIN-RELEASING-HORMONE NEURONAL CELL-LINE

Recent studies in several neuronal lineages suggest that extrinsic fac tors such as polypeptide growth factors regulate various stages of neu ronal development, from initial commitment of multipotent progenitors to induction of specific gene expression that is characteristic of ter minal neuronal differentiation, In the present study, immortalized hyp othalamic neurons of the GT1-1 lineage were used to analyze proliferat ive, as well as morphological and molecular differentiation actions of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor-alpha. (TGF-alpha), and insulin-like growt h factor-I (IGF-I), These effects were compared with those induced by specific activators of protein kinase A and C pathways, which potently inhibited cell proliferation and gonadotropin-releasing hormone (GnRH ) gene expression, but stimulated morphological neuronal maturation as determined by the length and number of neurite outgrowth, bFGF exerte d a broad spectrum of stimulatory effects, increasing the rate of prol iferation measured both by the incorporation of H-3-thymidine and by c ell number, and parameters of terminal differentiation, such as neurit e outgrowth and induction of gene expression, bFGF stimulated the expr ession of the hybrid transgene-containing portions of the rat GnRH pro moter, In contrast, EGF, TGF-alpha, and IGF-I inhibited cell prolifera tion, while having subtle effects on neurite outgrowth, Thus, GT1-1 ce lls appear to be differentially responsive to distinct neurotrophic fa ctors, providing a model for studying the specific effects of neurotro phic factors on functional differentiation, migration, and connectivit y of hypothalamic neurons. (C) 1997 Wiley-Liss, Inc.