Role of insulin-like growth factor binding proteins in controlling IGF actions.
The insulin-like growth factors (IGF) stimulate growth in multiple connective tissue cell types. The capacity of IGF-I and -II to access cell surface receptors is controlled by insulin-like growth factor binding proteins (IGFBPs). Connective tissue cells synthesize four of the IGFBPs (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 specific serine proteases that are produced for each form of IGFBP. Following cleavage, the IGFBPs have reduced affinity for IGF-I and -II, thus allowing release to receptors. Variables that regulate the amount of proteolysis have been shown to regulate IGF action. In addition to being proteolytically cleaved, three forms of IGFBPs (IGFBP-2, -3 and -5) can associate with extracellular matrix (ECM). In the case of IGFBP-5 binding to ECM, its affinity is lowered substantially allowing IGF to better equilibrate with the receptors. This event results in a potentiation of IGF-I action on fibroblasts and smooth muscle cells (SMC). In summary, IGFBPs are important molecules for regulating the bioavailability of IGF-I and -II to receptors. Understanding the variables that regulate their abundance may lead to a better understanding of the factors that regulate IGF action in skeletal tissues.
Clemmons
D R
DR
Division of Endocrinology, The University of North Carolina, Chapel Hill 27599-7170, USA.
D000818:Animals; D003239:Connective Tissue Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism*
D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D012697:Serine Endopeptidases