ROLE OF INSULIN-LIKE-GROWTH-FACTOR BINDING-PROTEINS IN CONTROLLING IGF ACTIONS

The insulin-like growth factors (IGF) stimulate growth in multiple con nective tissue cell types. The capacity of IGF-I and -II to access cel l surface receptors is controlled by insulin-like growth factor bindin g: proteins (IGFBPs). Connective tissue cells synthesize four of the I GFBPs (IGFBP-2 through -5). Synthesis is controlled by growth hormone and several other growth factors. In addition to regulating synthesis, other variables regulate the abundance of the IGFBPs including specif ic serine proteases that are produced for each form of IGFBP. Followin g cleavage, the IGFBPs have reduced affinity for TGF-T and -II, thus a llowing release to receptors. Variables that regulate the amount of pr oteolysis have been shown to regulate IGF action. In addition to being proteolytically cleaved, three forms of IGFBPs (IGFBP-2; -3 and -5) c an associate with extracellular matrix (ECM). In the case of IGFBP-5 b inding to ECM, its affinity is lowered substantially allowing IGF to b etter equilibrate with the receptors. This event results in a potentia tion of IGF-I action on fibroblasts and smooth muscle cells (SMC). In summary, IGFBPs are important molecules for regulating the bioavailabi lity of IGF-I and -II to receptors. Understanding the variables that r egulate their abundance may lead to a better understanding of the fact ors that regulate IGF action in skeletal tissues. (C) 1998 Elsevier Sc ience Ireland Ltd. All rights reserved.