Ballotti R, Nielsen F C, Pringle N, Kowalski A, Richardson W D, Van Obberghen E, Gammeltoft S
INSERM U 145, Faculté de Médicine, Université de Nice, France.
EMBO J. 1987 Dec 1;6(12):3633-9. doi: 10.1002/j.1460-2075.1987.tb02695.x.
Gene expression, receptor binding and growth-promoting activity of insulin-like growth factor I (IGF I) was studied in cultured astrocytes from developing rat brain. Northern blot analysis of poly(A)+ RNAs from astrocytes revealed an IGF I mRNA of 1.9 kb. Competitive binding and receptor labelling techniques revealed two types of IGF receptor in astroglial cells. Type I IGF receptors consist of alpha-subunits (Mr 130,000) which bind IGF I with significantly higher affinity than IGF II, and beta-subunits (Mr 94,000) which show IGF I-sensitive tyrosine kinase activity. Type II IGF receptors are monomers (Mr 250,000) which bind IGF II with three times higher affinity than IGF I. Both types of IGF receptor recognize insulin weakly. DNA synthesis measured by cellular thymidine incorporation was stimulated 2-fold by IGF I and IGF II. IGF I was more potent than IGF II, and both were significantly more potent than insulin. Our findings suggest that IGF I is synthesized in fetal rat astrocytes and acts as a growth promoter for the same cells by activation of the type I IGF receptor tyrosine kinase. We propose that IGF I acts through autocrine or paracrine mechanisms to stimulate astroglial cell growth during normal brain development.
在发育中大鼠脑的培养星形胶质细胞中，研究了胰岛素样生长因子I（IGF I）的基因表达、受体结合及促生长活性。对星形胶质细胞的聚腺苷酸加尾RNA（poly(A)+ RNA）进行Northern印迹分析，发现了一条1.9 kb的IGF I mRNA。竞争性结合和受体标记技术揭示了星形胶质细胞中有两种类型的IGF受体。I型IGF受体由α亚基（分子量130,000）和β亚基（分子量94,000）组成，α亚基与IGF I的结合亲和力显著高于IGF II，β亚基具有IGF I敏感的酪氨酸激酶活性。II型IGF受体是单体（分子量250,000），其与IGF II的结合亲和力比IGF I高3倍。两种类型的IGF受体对胰岛素的识别能力都较弱。通过细胞胸苷掺入法测定的DNA合成受到IGF I和IGF II的2倍刺激。IGF I比IGF II更有效，且两者都比胰岛素显著更有效。我们的研究结果表明，IGF I在胎鼠星形胶质细胞中合成，并通过激活I型IGF受体酪氨酸激酶作为相同细胞的生长促进剂。我们提出，IGF I通过自分泌或旁分泌机制在正常脑发育过程中刺激星形胶质细胞生长。
