Insulin-like growth factors in pediatric health and disease.

S THE introduction of the somatomedin hypothesis by Daughaday et al. (1) almost a half-century ago, our understanding of the insulin-like growth factor (IGF) system has evolved considerably. This evolution, from one of a simple pituitary-dependent growth factor secreted from liver to a ubiquitous and complex family of ligands, receptors, and binding proteins, has been spurred by advances in both protein biochemistry and, more recently, with the advent of the powerful tools of molecular biology. IGF-I and IGF-II are essential for normal growth and development. In tissue and organ systems that have fully differentiated, on the other hand, they play important roles in the homeostatic mechanisms associated with the normal function and maintenance of those tissues (2). Both IGF-I and IGF-II have been implicated in disease progression, either secondarily as the result of altered expression inducing abnormal growth and/or physiology (e.g. renal hypertrophy and deteriorating retinopathy during diabetes) or as one of the primary causative factors of the disease (e.g. overexpression in certain cancers and pediatric overgrowth disorders). This review discusses the normal physiology of the IGF system and describes some examples of pediatric diseases associated with alterations in this system and the possible therapeutic implications due to the availability of recombinant human IGF-I (rhIGF-I).