Physiology of the IGF system

Abstract

The insulin-like growth factors (IGFs) comprise a complex regulation system with two growth factors, cell-surface receptors, 6 specific high affinity IGF binding proteins (IGFBP1-6), IGFBP-proteases, as well as other IGFBP-interacting molecules. Although the IGFs and their signalling receptor closely resemble the peptide hormone (after which they were named) and its cell receptor; their modus operandi is very different from that of traditional peptide hormones. The IGFs are not stored within cells of a specific tissue but are present at very high levels throughout the body. They circulate at total concentrations approximately 1000 times higher than that of most peptide hormones and although tissue levels are somewhat lower, they are still present in vast excess compared to that required for maximal cellular stimulation. These high levels are maintained due to their association with the IGFBPs, which dramatically slow their clearance. The IGFBPs bind the IGFs with greater affinity than their cell surface receptors, enabling them to tightly control tissue activity. The IGFBP proteases modify the IGFBPs, lowering the affinity with which they bind IGFs. In the tissues the IGFs are important regulators of cell survival, growth, metabolism and differentiated function; the complex system confers specificity on these actions.