Molecular physiology, pathology, and regulation of the growth hormone/insulin-like growth factor-I system

Since the somatomedin hypothesis of growth hormone (GH) action was first formulated nearly 50 years ago, the key roles of both GH and insulin-like growth factor (IGF)-I in human growth have been confirmed and extended to include local effects on tissue maintenance and repair. More recent insights have revealed a dark side to the GH/IGF-I signaling system. Both proteins have been implicated as potential contributing factors in selected human cancers, and normal activity through this signaling pathway has been linked to diminished lifespan in experimental animals. This review highlights both the positive and negative aspects of the GH/IGF-I-growth pathway. The overall goal is to reinforce the need for more complete understanding of the mechanisms of signaling and action of GH and IGF-I, in order to separate, if possible, the potentially beneficial outcomes on growth and on tissue maintenance and repair from deleterious effects on cancer risk and lifespan.