New insights into growth hormone’s actions on the macrophage: implications for non-growth-related actions of growth hormone

hormonal and metabolic factors, including blood glucose levels, exercise, sex hormones, glucocorticoids and thyroid hormone. At the cellular level, the pleiotropic action of GH is elicited by its interaction with the GH receptor (GHR). GHR belongs to class I cytokine receptor superfamily that includes receptors for PRL, leptin and interleukins. The predicted molecular mass of GHR is ~70 kDa. An initiating event in this interaction is the activation of janus kinase 2 (JAK2), a GHR-associated tyrosine kinase. According to the original model, a single molecule of GH sequentially binds to two GHRs to induce dimer formation, which then increases the affinity of each GHR for JAK2. However, this original concept was revised recently by a study, which indicates GHRs either exist as a dimer2 or as a heterodimer with the prolactin receptor3 and that GH binding brings about a conformational change in the dimer that is important for the postreceptor signalling cascade, including activation of JAK2. Activated JAK2 phosphorylates itself and also the tyrosine residues in the cytoplasmic domain of GHR. These phosphotyrosines are thought to form high-affinity binding sites that recruit a variety of signalling proteins containing phosphotyrosine-binding domains, including signal transducers and activators of transcription (STAT) family proteins. The activated GHR–JAK2 complex can phosphorylate at least four members of the STAT family (STATs 1, 3, 5A and 5B), leading to their dimerisation, nuclear translocation and activation of transcription. Another pathway important in GH-regulated gene transcription is the mitogen-activated Abstract Introduction Growth hormone, besides being essential for post-natal growth in mammals, affects the metabolism of fat, protein and carbohydrates. At cellular level, the pleiotropic actions of growth hormone are due to its interaction with growth hormone receptor, followed by activation of the janus kinase 2–signal transducers and activators of transcription signalling cascade. The effects of growth hormone have been most intensely investigated in tissues such as liver, bone, muscle and adipocytes, in which growth hormone receptor expression is abundant, and are thus considered canonical targets of growth hormone action. However, recent studies on biological effects and physiological relevance of growth hormone action in non-canonical targets such as blastocysts, cardiomyocytes, colonic epithelium, glomerular podocytes and macrophages argue the importance of non-growth-related functions of growth hormone. In this review, we discuss immunomodulatory and metabolic effects of growth hormone on the macrophages. This review also highlights the role of growth hormone on macrophage migration, alternative activation and paracrine effect on adipocyte differentiation. Conclusion As we expand our knowledge about the role of growth hormone on regulating the components of immune system and metabolism, it may be possible to exploit the new information to enhance host resistance to infection, improve sensitivity to insulin and prevent atherosclerosis in conditions such as acquired immunodeficiency syndrome, short bowel syndrome, Prader-Willi and lipodystrophy syndromes.