REGULATORY ACTIONS OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEINS

The six insulin-like growth factor-binding proteins (IGFBPs) are impor tant regulators of insulin-like growth factor (IGF) action, Circulatin g high molecular weight complexes that contain IGF and IGFBP-3 restric t IGF bioavailability, and excess IGFBPs inhibit IGF action by forming biologically inactive complexes. IGFs can be released front these com plexes by proteolysis. Potentiation of IGF activity might occur under specific circumstances, and involves the slow dissociation of IGFs fro m IGFBP complexes localized in the pericellular space, whose affinity has been reduced by dephosphorylation or association with the cell sur face or extracellular matrix. Several IGFBPs or IGFBP fragments also h ave activities that do not involve IGFs or IGF receptors. The mechanis ms by which IGFBPs regulate IGF action and exert their independent act ions will be examined.