Mechanisms of Modulation of IGF's Action

最近的证据，来自使用基因敲除或过表达小鼠的研究，表明胰岛素样生长因子（IGFs）和/或其受体是哺乳动物的正常发育和生长所必需的。此外，在许多细胞类型中，IGFs已显示具有多种生物活性，包括诱导细胞增殖和分化、抑制细胞凋亡和维持细胞功能的能力。IGFs在血浆中循环，并作为与几种特异性结合蛋白（IGFBPs）的复合物在整个细胞外空间循环。目前认为IGFBPs控制IGFs的半衰期并调节IGFs的可用性;然而，它们的生理作用仍不清楚。尽管IGFs的生物活性丰富多样，但IGFs的体外生物学效应相对较弱，并且通常无法证明，除非存在其他激素或生长因子。在此背景下，进行本研究以确定细胞外和 ...更多信息 调节IGFs生物活性的细胞内机制，以响应其他激素或生长因子和不同的生理条件。首先，在不同生理条件下，我们分析了IGFs和IGFBPs的产生，血清中IGFs和IGFBPs之间的相互作用，IGF受体的表达。我们的研究结果表明，IGF/IGFBP/IGF受体的表达以不同的方式进行调节，从而产生合理的IGFs生物活性，以响应每种生理情况。此外，在内分泌细胞中，我们证明了营养激素通过细胞内信号的串扰机制引发细胞对IGF-I的反应。在肝细胞中，观察到胰岛素和cAMP之间的类似增强作用，这表明串扰机制对于一般控制胰岛素样活性非常重要。从一系列这些数据中，我们得出结论，IGF生物活性是由以下过程调节的：1）IGF产生，2）IGFBPs产生，3）IGF和IGFBPs之间的相互作用，4）IGF受体表达，和5）IGF信号转导，响应于其他激素或生长因子以及生理条件。这种调节必须是哺乳动物正常发育和生长所必需的。少

Recent evidence, derived from studies using knock-out or overexpression mice, indicates that insulinlike growth factors (IGFs) and/or their receptors are essential for the normal development and growth of mammals. Further, in many cell types IGFs have been shown to possess a variety of bioactivities, including the ability to induce cell proliferation and differentiaton, to inhibit cell apoptosis, and to maintain cell functio. IGFs circulates in the plasma and throughout the extracellular space as a complex with several specific binding proteins (IGFBPs). IGFBPs are believed at present to control half-lives of IGFs and modulate IGFs availability ; however, their physiological roles are still unclear. Despite the profuseness and diversity of IGFs bioactivities, the in vitro biological effects of IGFs are relatively weak and often are not demonstrable except in the presence of other hormones or growth factors. From this background, this study was undertaken to determine extracellular and … More intracellular mechanisms to modulate IGFs bioactivities in response to other hormones or growth factors, and different physiological conditions. Firstly, under various physiological conditions, we analyzed production of IGFs and IGFBPs interaction between IGFs and IGFBPs in serum, expression of IGF receptors. Our results suggested that expression of IGF/IGFBP/IGF receptors is regulated in different manners, resulting in reasonable IGFs bioactivities in response to each physiological situation. In additions, in endocrine cells, we demonstrated that tropic hormones prime cells to respond to IGF-I through cross-talk mechanisms of the intracellular signals. In liver cells, the similar potentiation between insulin and camp was observed, suggesting that the cross-talk mechanisms are very important to control insulin-like activities in general. From a series of these data, we concluded that IGF bioactivities are modulated by the process of 1) IGFs production, 2) IGFBPs production, 3) interaction between IGFs and IGFBPs, 4) IGF receptor expression, and 5) IGF signal transduction, in response to other hormones or growth factors as well as physiological conditions. This modulation must be required for normal development and growth of mammals. Less