Regulatory Actions of Insulin-like Growth Factor-binding Proteins

The six insulin-like growth factor-binding proteins (IGFBPs) are important regulators of insulin-like growth factor (IGF) action. Circulating high molecular weight complexes that contain IGF and IGFBP-3 restrict IGF bioavailability, and excess IGFBPs inhibit IGF action by forming biologically inactive complexes. IGFs can be released from these complexes by proteolysis. Potentiation of IGF activity might occur under specific circumstances, and involves the slow dissociation of IGFs from IGFBP complexes localized in the pericellular space, whose affinity has been reduced by dephosphorylation or association with the cell surface or extracellular matrix. Several IGFBPs or IGFBP fragments also have activities that do not involve IGFs or IGF receptors. The mechanisms by which IGFBPs regulate IGF action and exert their independent actions will be examined.