Insulin-Like Growth Factor Binding Protein Control Secretion and Mechanisms of Action
The insulin-like growth factors are present in extracellular fluids bound to high affinity soluble binding proteins. This localization of IGF-I and II in the pericellular microenvironment in association with IGF binding proteins suggests a role for these proteins in controlling the amount of IGF that is transported to specific cell types and the amount of growth factor that is available to associate with type I and II IGF receptors. This theory has recently been strengthened by the observation that each of the IGF binding proteins that have been purified has an affinity constant that is higher than the type I IGF receptor.1 Therefore these proteins have the capacity to partition IGF-I and II between receptors and the extracellular fluid compartment. Other proposed functions of the IGF binding proteins include acting as a high affinity carriers in plasma and preventing uncontrolled efflux of the IGFs from the vascular space. In blood IGF-I and II form a 150 kilodalton complex with IGF binding protein-3 (IGFBP-3)2. The complex is not transported across intact capillaries and forms a reservoir of IGF that is available for utilization by peripheral tissues. Since IGF-I and II are believed to be secreted into blood and utilized by peripheral tissues at a relatively constant rate, the binding protein in the vascular compartment may provide a means for maintaining a sustained amount of growth factor that is available for transport into extracellular fluids.
KeywordsGrowth Hormone Decidual Cell Acid Labile Subunit Extracellular Fluid Compartment Pericellular Microenvironment
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