The growth hormone signaling system: Insights into coordinating the anabolic and catabolic actions of growth hormone

Although growth hormone (GH) is a multifunctional factor that coordinates various aspects of feeding, reproduction, osmoregulation, and immune system function, perhaps two of its most studied actions are the regulation of growth and metabolism, particularly lipid metabolism. In this review, we describe the major growth-promoting and lipid metabolic actions of GH and then discuss how the GH system regulates these actions. Numerous intrinsic and extrinsic factors provide information about the metabolic status of the organism and influence the production of release of GH. The actions of GH are mediated by GH receptors (GHR), which are widely distributed among tissues. Teleosts possess multiple forms of GHRs that arose through the evolution of this group. Modulation of tissue responsiveness to GH is regulated by molecular and functional expression of GHRs, and in teleosts GHR subtypes, by various factors that reflect the metabolic and growth status of the organism, including nutritional state. The action of GH is propagated by the linkage of GHRs to several cellular effector systems, including JAK-STAT, ERK, PI3K-Akt, and PKC. The differential activation of these pathways, which is governed by nutrient status, underlies GH stimulation of growth or GH stimulation of lipolysis. Taken together, the multi-functional actions of GH are determined by the distribution and abundance of GHRs (and GHR subtypes in teleosts) as well as by the GHR-effector system linkages.