Cohick W S, Clemmons D R
Department of Medicine, University of North Carolina, Chapel Hill 27599.
Annu Rev Physiol. 1993;55:131-53. doi: 10.1146/annurev.ph.55.030193.001023.
The recent availability of reagents to study the IGFs, their receptors, and binding proteins has led to an explosive growth in the study of IGF physiology. However, most studies to date have been descriptive, and studies delineating mechanisms of action are limited. It is apparent that most organ systems synthesize several components of the IGF system necessary for IGF to function in an autocrine or paracrine fashion and that regulation of this system occurs at the local level. However, the relative importance of locally produced IGF vs circulating IGF remains unclear. The mechanisms by which the IGFBPs modulate IGF activity are crucial to understanding this system, and identification of specific roles for each of these proteins will be required. Of critical importance is the identity of the intracellular signal transduction system by which the IGF receptor mediates the effects of the IGFs, and the delineation of mechanisms by which the IGFBPs interact with the receptor at the cellular level. It is also of interest to determine what role, if any, the IGF-II receptor plays in mediating the growth-promoting effects of the IGFs. The ubiquitous distribution of the IGFs, IGFBPs, and IGF receptors indicates that they may play a role in the regulation of coordinate growth among several tissues and cell types. Understanding the mechanisms by which these components interact to coordinate growth responses between different cell types should greatly enhance our understanding of normal growth and development.
近年来,用于研究胰岛素样生长因子(IGFs)、其受体及结合蛋白的试剂已问世,这使得IGF生理学研究呈爆发式增长。然而,迄今为止,大多数研究都只是描述性的,而阐明作用机制的研究有限。显然,大多数器官系统都会合成IGF系统的多种成分,这些成分是IGF以自分泌或旁分泌方式发挥作用所必需的,而且该系统的调节发生在局部水平。然而,局部产生的IGF与循环IGF的相对重要性仍不清楚。胰岛素样生长因子结合蛋白(IGFBPs)调节IGF活性的机制对于理解该系统至关重要,需要确定这些蛋白各自的具体作用。至关重要的是确定IGF受体介导IGFs效应的细胞内信号转导系统的特性,以及阐明IGFBPs在细胞水平上与受体相互作用的机制。确定IGF-II受体在介导IGFs的促生长作用中是否发挥作用(若有作用则确定其作用)也很有意思。IGFs、IGFBPs和IGF受体的广泛分布表明,它们可能在调节多种组织和细胞类型之间的协同生长中发挥作用。了解这些成分相互作用以协调不同细胞类型之间生长反应的机制,应能极大地增进我们对正常生长和发育的理解。