Serum insulin-like growth factors and insulin-like growth factor-binding proteins: clinical implications

The last decade has been characterized by a major investigative thrust into the physiology of two unique but ubiquitous peptides, insulin-like growth factor (IGF)-I and IGF-II. The regulatory systems that control the tissue bioactivity of the IGFs have been delineated, and subcellular signaling mechanisms have been clarified. Clearly, both tissue and circulating growth factor concentrations are important in defining the relationship between IGF-I and cell activity. Bone, liver, and circulatory IGF-I have received the most attention by investigators, in part because of the ease of measurement and the interaction with disease states such as osteoporosis. More recently, attention has focused on the role IGF-I plays in neoplastic transformation and growth. Two large prospective observational studies have demonstrated greater risk for prostate and breast cancer associated with high circulating concentrations of IGF-I. Animal models and in vitro studies confirm that there is a close, albeit complex, interaction between IGF-I signaling and bone turnover. This report will focus on: (a) IGF physiology, including IGF ligands, binding proteins, and proteases; (b) the relationship between IGF-I and bone mass in respect to risk for osteoporosis; (c) the heritable regulation of the IGF-I phenotype; and (d) the association between serum IGF-I and cancer risk. The IGFs remain a major area for basic and clinical investigations; future studies may define both diagnostic and therapeutic roles for these peptides or their related proteins in several disease states.