Insulin-like growth factor 1 receptor signaling induced by supraphysiological doses of IGF-1 in human peripheral blood lymphocytes

Insulin-like growth factor-1 (IGF-1) mediates some of growth hormone (GH) anabolic functions through its receptor, IGF1R. Following ligand binding, intracellular signaling pathways are activated favouring proliferation, cell survival, tissue growth, development and differentiation. IGF-1 is included in the World Anti-Doping Agency Prohibited List. While the evidences for IGF-1 as performance enhancing substrate in healthy humans are still weak, clinical studies demonstrated that the endogenous GH/IGF-1 excess is associated with cardiovascular implications. Previously, we demonstrated that human peripheral lymphocytes (PBL) represent a suitable system to identify a gene signature, related to dihydrotestosterone (DHT) or IGF-1 abuse, independent from the type of sport. In addition, in a proteomic study, we demonstrated that DHT hyperdosage affects cell motility and apoptosis. Here we investigate the doping action of IGF-1 by means of a differential proteomic approach and specific protein arrays, revealing an active cytoskeletal reorganization mediated by Stat-1; moreover, IGF-1 stimulation produces a sustained activation of different signaling pathways as well as an overproduction of cytokines positively related to immune response and inflammation. In conclusion, these data indicate that, following IGF-1 hyperdosage, circulating PBL could be more prone to transendothelial migration.