Mapping the growth hormone–Stat5b–IGF-I transcriptional circuit

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) exert powerful influences on somatic growth, metabolism, and tissue repair, and have been implicated in aging and carcinogenesis. Since the formulation of the somatomedin hypothesis over 50 years ago, GH and IGF-I have been linked intimately to one another. Recent studies have established that GH potently stimulates IGF-I gene transcription, and through this mechanism controls production of IGF-I. A key mediator of the GH–IGF-I biosynthetic pathway is the latent transcription factor Stat5b. This review summarizes the potentially complex mechanistic relationship between GH action, Stat5b, and IGF-I gene activation, and suggests that Stat5b may have a broad role in mediating IGF-I gene regulation in response to diverse physiological inputs.