Abnormalities of IGF-I signaling in the pathogenesis of diseases of the bone, brain, and fetoplacental unit in humans

Department of Emergency and Organ Transplantation, Section on Internal Medicine, Endocrinology, and Metabolic Diseases, University of Bari, Bari, Italy Submitted 20 May 2008 ; accepted in final form 15 August 2008 ABSTRACT IGF-I action is essential for the regulation of tissue formation and remodeling, bone growth, prenatal growth, brain development, and muscle metabolism. Cellular effects of IGF-I are mediated through the IGF-I receptor, a transmembrane tyrosine kinase that phosphorylates intracellular substrates, resulting in the activation of multiple intracellular signaling cascades. Dysregulation of IGF-I actions due to impairment in the postreceptor signaling machinery may contribute to multiple diseases in humans. This article will review current information on IGF-I signaling and illustrate recent results demonstrating how impaired IGF-I signaling and action may contribute to the pathogenesis of human diseases, including osteoporosis, neurodegenerative disorders, and reduced fetal growth in utero. insulin-like growth factor I; insulin-like growth factor I receptor; osteoblasts; osteoporosis; neurodegenerative disorders; placenta; intrauterine growth restriction Address for reprint requests and other correspondence: F. Giorgino, Dept. of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, and Metabolic Diseases, Univ. of Bari, Piazza Giulio Cesare, 11, I-70124 Bari, Italy (e-mail: f.giorgino{at}endo.uniba.it )