Insulin-like growth factor binding proteins: Structural and molecular relationships

The insulin-like growth factors (IGFs) are important metabolic and mitogenic factors involved in cell growth and metabolism. IGF-I and -II belong to a family of peptide hormones that include relaxin and insulin, and they share a high degree of structural similarity with proinsulin. They are produced in the liver and multiple other tissues, and are partially growth hormone dependent. These peptides interact with specific high affinity receptors, designated as type I and type II IGF receptors, as well as with the insulin receptor. IGFs have direct effects on somatic growth and on the proliferation of many tissues and cell types, both in vivo and in vitro. IGF-I is currently thought to be the main mediator of the growth promoting actions of human growth hormone and IGFs also have a profound effect on carbohydrate and lipid metabolism, distinct from that of insulin. A recently recognized class of proteins which have high affinity and specificity for the IGFs, the IGF binding proteins (designated as IGFBPs; Ballard et al., 1989; Rosenfeld et al., 1990), have been shown to be involved in modulation of the proliferative and mitogenic effects of IGFs on cells. The molecular mechanisms involved in the interaction of the IGFBPs with the IGFs and their receptors remain unclear, but it is certain that a full understanding of the actions of IGF in vivo will require the characterization of these binding proteins.