Molecular mechanism of growth hormone action

Although the ability of growth hormone (GH) to stimulate body growth and regulate metabolism has been recognized for many years, only recently has insight been gained into the molecular mechanisms by which binding of GH to its receptor (GHR) elicits its diverse effects. This review provides an overview of what is currently known about the molecular mechanisms of GH action. The model presented is one in which GH binding to two GHRs causes dimerization of GHR, activation of the GHR-associated JAK2 tyrosine kinase, and tyrosyl phosphorylation of both JAK2 and GHR. These events recruit and/or activate a variety of signaling molecules, including MAP kinases, insulin receptor substrates, phosphatidylinositol 3' phosphate kinase, diacylglycerol, protein kinase C, intracellular calcium, and Stat transcription factors. These signaling molecules contribute to the GH-induced changes in enzymatic activity, transport function, and gene expression that ultimately culminate in changes in growth and metabolism.