MOLECULAR MECHANISM OF GROWTH-HORMONE ACTION

Although the ability of growth hormone (GH) to stimulate body growth a nd regulate metabolism has been recognized for many years, only recent ly has insight been gained into the molecular mechanisms by which bind ing of GH to its receptor (GHR) elicits its diverse effects. This revi ew provides an overview of what is currently known about the molecular mechanisms of GH action. The model presented is one in which GH bindi ng to two GHRs causes dimerization of GHR, activation of the GHR-assoc iated JAK2 tyrosine kinase, and tyrosyl phosphorylation of both JAK2 a nd GHR. These events recruit and/or activate a variety of signaling mo lecules, including MAP kinases, insulin receptor substrates, phosphati dylinositol 3' phosphate kinase, diacylglycerol, protein kinase C, int racellular calcium, and Stat transcription factors. These signaling mo lecules contribute to the GH-induced changes in enzymatic activity, tr ansport function, and gene expression that ultimately culminate in cha nges in growth and metabolism.