Molecular and Cellular Aspects of Insulin-like Growth Factor Action

This chapter discusses the molecular and cellular aspects of insulin-like growth factor (IGF) action. The IGF-I and IGF-II are pluripotent factors that regulate growth, differentiation, and the maintenance of differentiated function in numerous tissues and in specific cell types. Both IGFs are produced in largest amounts by the liver and are secreted into the circulation, where they function as classical endocrine agents by interacting with specific cell-surface receptors present on target tissues. The widespread distribution of IGF receptors, and the production and secretion of the IGFs themselves by almost all extrahepatic tissues, suggests that these factors employ autocrine and paracrine modes of action. The actions of the IGFs are also influenced by a family of IGF binding proteins that are found in the circulation and in extracellular fluids; these proteins may have positive or negative effects on IGF action through different mechanisms. The overall actions of these important molecules are governed by a complex interplay between ligands, receptors, and binding proteins. The levels and the regulation of each component contribute significantly to the ultimate biological effects manifested in a given situation.