Department of MedicineUNC School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
J Mol Endocrinol. 2018 Jul;61(1):T139-T169. doi: 10.1530/JME-18-0016. Epub 2018 Mar 21.
The IGF-binding protein family contains six members that share significant structural homology. Their principal function is to regulate the actions of IGF1 and IGF2. These proteins are present in plasma and extracellular fluids and regulate access of both IGF1 and II to the type I IGF receptor. Additionally, they have functions that are independent of their ability to bind IGFs. Each protein is regulated independently of IGF1 and IGF2, and this provides an important mechanism by which other hormones and physiologic variables can regulate IGF actions indirectly. Several members of the family are sensitive to changes in intermediary metabolism. Specifically the presence of obesity/insulin resistance can significantly alter the expression of these proteins. Similarly changes in nutrition or catabolism can alter their synthesis and degradation. Multiple hormones such as glucocorticoids, androgens, estrogen and insulin regulate IGFBP synthesis and bioavailability. In addition to their ability to regulate IGF access to receptors these proteins can bind to distinct cell surface proteins or proteins in extracellular matrix and several cellular functions are influenced by these interactions. IGFBPs can be transported intracellularly and interact with nuclear proteins to alter cellular physiology. In pathophysiologic states, there is significant dysregulation between the changes in IGFBP synthesis and bioavailability and changes in IGF1 and IGF2. These discordant changes can lead to marked alterations in IGF action. Although binding protein physiology and pathophysiology are complex, experimental results have provided an important avenue for understanding how IGF actions are regulated in a variety of physiologic and pathophysiologic conditions.
胰岛素样生长因子结合蛋白家族包含六个具有显著结构同源性的成员。它们的主要功能是调节 IGF1 和 IGF2 的作用。这些蛋白存在于血浆和细胞外液中，调节 IGF1 和 II 与 IGF1 型受体的结合。此外，它们具有独立于结合 IGF 能力的功能。每种蛋白都独立于 IGF1 和 IGF2 进行调节，这为其他激素和生理变量通过间接方式调节 IGF 作用提供了一个重要机制。该家族的几个成员对中间代谢的变化敏感。具体来说，肥胖/胰岛素抵抗的存在可以显著改变这些蛋白的表达。同样，营养或分解代谢的变化可以改变它们的合成和降解。多种激素，如糖皮质激素、雄激素、雌激素和胰岛素，调节 IGFBP 的合成和生物利用度。除了调节 IGF 与受体结合的能力外，这些蛋白还可以与细胞表面蛋白或细胞外基质中的蛋白结合，并且这些相互作用会影响多种细胞功能。IGFBPs 可以在细胞内运输，并与核蛋白相互作用，改变细胞生理学。在病理生理状态下，IGFBP 合成和生物利用度的变化与 IGF1 和 IGF2 的变化之间存在显著失调。这些不一致的变化会导致 IGF 作用的明显改变。尽管结合蛋白的生理学和病理生理学非常复杂，但实验结果为理解在各种生理和病理生理条件下 IGF 作用是如何调节的提供了一个重要途径。
