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Differential effects of basic fibroblast growth factor, epidermal growth factor, transforming growth factor‐α, and insulin‐like growth factor‐I on a hypothalamic gonadotropin‐releasing hormone neuronal cell line
Author(s) -
Ochoa Alejandra,
Domenzáin Clelia,
Clapp Carmen,
Martínez de la Escalera Gonzalo
Publication year - 1997
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19970915)49:6<739::aid-jnr8>3.0.co;2-8
Subject(s) - basic fibroblast growth factor , neurite , biology , epidermal growth factor , growth factor , fibroblast growth factor , transforming growth factor , microbiology and biotechnology , medicine , neurotrophic factors , endocrinology , neurotrophin , cellular differentiation , fibroblast growth factor receptor 4 , cell culture , fibroblast growth factor receptor , receptor , gene , genetics , in vitro
Recent studies in several neuronal lineages suggest that extrinsic factors such as polypeptide growth factors regulate various stages of neuronal development, from initial commitment of multipotent progenitors to induction of specific gene expression that is characteristic of terminal neuronal differentiation. In the present study, immortalized hypothalamic neurons of the GT1‐1 lineage were used to analyze proliferative, as well as morphological and molecular differentiation actions of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor‐α (TGF‐α), and insulin‐like growth 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 exerted a broad spectrum of stimulatory effects, increasing the rate of proliferation measured both by the incorporation of 3 H‐thymidine and by cell number, and parameters of terminal differentiation, such as neurite outgrowth and induction of gene expression. bFGF stimulated the expression of the hybrid transgene‐containing portions of the rat GnRH promoter. In contrast, EGF, TGF‐α, and IGF‐I inhibited cell proliferation, while having subtle effects on neurite outgrowth. Thus, GT1‐1 cells appear to be differentially responsive to distinct neurotrophic factors, providing a model for studying the specific effects of neurotrophic factors on functional differentiation, migration, and connectivity of hypothalamic neurons. J. Neurosci. Res. 49:739–749, 1997. © 1997 Wiley‐Liss, Inc.