How growth hormone controls growth, obesity and sexual dimorphism

Abstract

Understanding the molecular basis for the many actions of growth hormone (GH) has been challenging because many of these actions are only evident in vivo. Recently, STAT5b has emerged as a key GH signaling intermediate in the regulation of postnatal growth, adiposity and sexual dimorphism of hepatic gene expression. This realization is based on targeted disruption or mutation of the GH receptor and its signaling components, together with clinical studies of GH-insensitive mutants. Microarray analysis of liver from GH receptor and signal transducer and activation of transcription 5b (STAT5b)-deleted mice have identified a range of relevant transcripts regulated by the Janus kinase 2/STAT5b signaling pathway. In addition, many transcripts are regulated independently of STAT5b, presumably as a result of PtdIns 3-kinase, extracellular-regulated kinase and Src signaling by this pleiotropic cytokine receptor.