Growth hormone can act as a cytokine controlling survival and proliferation of immune cells: new insights into signaling pathways.

While growth hormone (GH) is classically defined as a peptide hormone, recent evidence supports a role for GH acting as a cytokine in the immune system under conditions of stress, counteracting immunosuppression by glucocorticoids. Lymphoid cells express the GH receptor, which belongs to the cytokine receptor superfamily, and GH can be produced by immune tissues, suggesting an autocrine/paracrine mode of action of GH. GH can act as a cytokine, promoting cell cycle progression of lymphoid cells and preventing apoptosis. These effects of GH were shown to be mainly mediated by the PI-3 kinase/Akt pathway and the transcription factor NF-kappaB. Expression of several cell cycle mediators, as well as Bcl-2, c-Myc and cyclin proteins were found to be regulated by GH. Survival of immune cells under conditions of stress was promoted by NF-kappaB. Thus, GH acts not only as a hormone but also as a cytokine, playing a potentially important role in immune system cells. Lastly, in this mini-review, we will discuss whether the discovery of these molecules in GH signaling pathways offers new insights into additional mechanisms of action whereby GH regulates apoptosis, proliferation and neoplastic transformation of cells of the immune system.