Duan C
Department of Biology, University of Michigan, Ann Arbor 48109-1048, USA.
J Nutr. 1998 Feb;128(2 Suppl):306S-314S. doi: 10.1093/jn/128.2.306S.
The insulin-like growth factors (IGF) are evolutionarily ancient growth factors present in all vertebrates. The central importance of IGF for normal development and growth has been illustrated by the severe growth-retarded phenotype exhibited by IGF-I, IGF-II or IGF-I receptor "knockout" mice. Although we know much about the gross effects of IGF on the overall size of the fetus and the clinical manifestations that result from fetal and neonatal deficiency of IGF (i.e., severe growth retardation leads to dwarfism), very little is known about the in vivo actions of IGF during embryogenesis at the cellular and molecular levels. Most research on the developmental role of IGF has relied on rodent models, and attempts to elucidate the molecular and cellular basis of IGF actions have been hampered by the inaccessibility of the mammalian fetus enclosed in the uterus. During the past decade, there has been growing support for the concept that the IGF have been highly conserved in all vertebrates. Both IGF-I and IGF-II are present in fish, and their structures are highly conserved. Human and fish IGF-I are equally potent in mammalian and fish bioassay systems. Insulin-like growth factor mRNA is found in all life stages of fish, ranging from unfertilized egg to adult. The temporal and spatial expression patterns of fish IGF-I seem to be similar to those in mammals. Nutritional status and growth hormone both have a profound effect on IGF-I expression in fish, as they do in mammals. These features suggest that the IGF system is highly conserved between teleost fish and mammals. Because fish embryos develop externally, they provide excellent animal models for understanding the regulatory roles of IGF, IGF receptor and IGF-binding proteins in vertebrate embryonic development. Current research on the developmental and nutritional roles of IGF in fish will undoubtedly contribute to knowledge of the basic physiology of vertebrates in general.
胰岛素样生长因子(IGF)是所有脊椎动物中存在的进化上古老的生长因子。IGF对正常发育和生长的核心重要性已通过IGF-I、IGF-II或IGF-I受体“敲除”小鼠表现出的严重生长迟缓表型得到说明。尽管我们对IGF对胎儿整体大小的总体影响以及胎儿和新生儿IGF缺乏导致的临床表现(即严重生长迟缓导致侏儒症)了解很多,但对于IGF在胚胎发生过程中细胞和分子水平的体内作用却知之甚少。关于IGF发育作用的大多数研究都依赖于啮齿动物模型,而阐明IGF作用的分子和细胞基础的尝试因子宫内哺乳动物胎儿难以接近而受到阻碍。在过去十年中,越来越多的人支持这样一种观点,即IGF在所有脊椎动物中高度保守。IGF-I和IGF-II在鱼类中都存在,并且它们的结构高度保守。人源和鱼源IGF-I在哺乳动物和鱼类生物测定系统中具有同等效力。胰岛素样生长因子mRNA在鱼类从未受精卵到成体的所有生命阶段都能找到。鱼类IGF-I的时空表达模式似乎与哺乳动物相似。营养状况和生长激素对鱼类IGF-I表达都有深远影响,就像它们对哺乳动物的影响一样。这些特征表明硬骨鱼和哺乳动物之间的IGF系统高度保守。由于鱼类胚胎在体外发育,它们为理解IGF、IGF受体和IGF结合蛋白在脊椎动物胚胎发育中的调节作用提供了极好的动物模型。目前关于IGF在鱼类发育和营养作用的研究无疑将有助于总体上了解脊椎动物的基本生理学知识。