Trophic effects of insulin-like growth factor-I on fetal rat hypothalamic cells in culture.
The hypothesis that insulin-like growth factor-I is a trophic factor for primary fetal rat hypothalamic cells was tested, since we previously reported a potent mitogenic effect of this peptide on virally-transformed hypothalamic cells. It was found that insulin-like growth factor-I produced significant and dose-dependent increases in the survival of fetal hypothalamic neurons in primary mixed glial/neuronal cultures. By 48 h in vitro, cultures treated with insulin-like growth factor-I (6 nM) had twice as many neurite-bearing cells as controls, while by day 15 a five-fold difference was present. The peptide was similarly active in promoting neuronal survival in neuron-enriched (98% neurons) hypothalamic cultures. Mixed hypothalamic cultures had specific binding sites for insulin-like growth factor-I. In addition, the neurons grown in the presence of insulin-like growth factor-I had a more differentiated morphology and had significantly higher levels of protein kinase C, an enzyme that increases during neurite formation and synaptogenesis. Finally, glial-enriched cultures (greater than 99% glial cells) obtained from the fetal hypothalamus showed increased [3H]thymidine incorporation in response to insulin-like growth factor-I. These results further support the contention that insulin-like growth factor-I is a neurotrophic factor and suggest that it may participate in the normal development of the hypothalamus by increasing neuronal survival/differentiation and stimulating glial growth.
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06510.
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Torres-Aleman
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Naftolin
R J
RJ
Robbins
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology; D005333:Fetus; D007031:Hypothalamus / Q000166:cytology* / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013002:Somatomedins / Q000494:pharmacology*
D007328:Insulin; D009419:Nerve Tissue Proteins; D013002:Somatomedins; D003561:Cytarabine; D015240:Phorbol 12,13-Dibutyrate; D007334:Insulin-Like Growth Factor I; D011493:Protein Kinase C