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 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-alpha (TGF-alpha), 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 3H-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-alpha, 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.
Ochoa
A
A
Neurobiology Center, National University of México, Juriquilla, Querétaro.
Domenzáin
C
C
Clapp
C
C
Martínez de la Escalera
G
G
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics; D006062:Gonadotropins / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology*; D007031:Hypothalamus / Q000166:cytology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000201:enzymology / Q000648:ultrastructure; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D019076:Transgenes / Q000502:physiology; D014316:Tritium
D002273:Carcinogens; D006062:Gonadotropins; D006133:Growth Substances; D016211:Transforming Growth Factor alpha; D014316:Tritium; D016222:Fibroblast Growth Factor 2; D005576:Colforsin; D007987:Gonadotropin-Releasing Hormone; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine