The Role of Insulin-Like Growth Factor Binding Proteins in Controlling the Expression of IGF Actions
Although the insulin-like growth factors are secreted into blood and transported to peripheral tissues where they can act as traditional endocrine hormones, they are also synthesized and secreted by many types of cells and may exert their effects in the local microenvironment by autocrine or paracrine regulatory mechanisms. Specifically, IGF-I mRNA has been detected by in situ hybridization in connective tissue cells in several human tissues1. This mRNA appears to be translated and the peptide secreted since several types of cells in culture, such as fibroblasts, have been shown to secrete IGF-I2,3. Furthermore, blocking the binding of cell-secreted IGF-I to the type I IGF receptor will block mitogenic response in the fibroblasts that constitutively synthesize this peptide4. These data suggest that IGF-I is made by the connective tissue cell types within organs, and is secreted into interstitial fluids. Following secretion IGF-I not only binds to receptors on fibroblasts but it can bind also to receptors on cells of epithelial origin that contain receptors but do not contain IGF-I mRNA. Immunocytochemical localization studies have shown IGF-I to be present on the surfaces of many cell types that apparently do not synthesize and secrete this peptide5.
KeywordsGrowth Hormone Human Amniotic Fluid Placental Protein Somatomedin Binding Protein Connective Tissue Cell Type
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