Torres-Aleman I, Naftolin F, Robbins R J
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06510.
Int J Dev Neurosci. 1989;7(2):195-202. doi: 10.1016/0736-5748(89)90069-5.
Recent evidence indicates that the insulin-like family of peptides may act as endogenous trophic factors in the central nervous system. To further examine this possibility we have investigated the effects of three insulin-like peptides on the in vitro growth of fetal hypothalamic cell lines. Two virally transformed rat hypothalamic cell lines which have been developed in our laboratory (A-6 and F-12) were used. Cells were plated at varying densities and cultured in the presence or absence of either insulin-like growth factor I (IGF-I), insulin, or multiplication stimulating activity (MSA or IGF-II), in serum-free medium for 1 wk. Cell growth was assessed by counting or by measuring cellular incorporation of 3H-thymidine. Of the three peptides tested IGF-I was the most potent in eliciting cell growth. Insulin also stimulated growth of both cell lines, but was 100 times less potent for A-6 cells while it was equipotent with IGF-I in F-12 cells. MSA had no effect on either cell line. Both IGF-I and insulin showed dose-response effects in increasing cell growth. We also found that the two cell lines had the greatest response to IGF-I at low cell densities. Finally, time-course experiments suggested that a continued presence of the peptide is essential for the growth-promoting effects. We conclude that IGF-I is a potent growth factor for virally transformed cell lines derived from the rat fetal hypothalamus. Since both IGF-I immunoreactivity and IGF-I receptors have been located in this diencephalic area these results suggest that IGF-I may constitute a mitogenic signal for hypothalamic cells during neurogenesis.
最近有证据表明，胰岛素样肽家族可能作为中枢神经系统中的内源性营养因子发挥作用。为了进一步研究这种可能性，我们研究了三种胰岛素样肽对胎儿下丘脑细胞系体外生长的影响。使用了我们实验室培养的两种病毒转化大鼠下丘脑细胞系（A - 6和F - 12）。将细胞以不同密度接种，在无血清培养基中于有或无胰岛素样生长因子I（IGF - I）、胰岛素或增殖刺激活性物质（MSA或IGF - II）的情况下培养1周。通过计数或测量3H - 胸腺嘧啶核苷的细胞掺入量来评估细胞生长。在所测试的三种肽中，IGF - I在促进细胞生长方面最有效。胰岛素也刺激了两种细胞系的生长，但对A - 6细胞的效力比IGF - I低100倍，而在F - 12细胞中它与IGF - I效力相当。MSA对两种细胞系均无影响。IGF - I和胰岛素在促进细胞生长方面均呈现剂量反应效应。我们还发现，两种细胞系在低密度时对IGF - I的反应最大。最后，时间进程实验表明，肽的持续存在对于其促生长作用至关重要。我们得出结论，IGF - I是源自大鼠胎儿下丘脑的病毒转化细胞系的一种有效生长因子。由于在这个间脑区域已发现IGF - I免疫反应性和IGF - I受体，这些结果表明IGF - I可能在神经发生过程中构成下丘脑细胞的有丝分裂信号。
