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

Abstract

Insulin-like growth factor-1 (IGF-1) mediates some of growth hormone anabolic functions through its receptor, IGF-1R. 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 evidence for IGF-1 as performance-enhancing substrate in healthy humans is still weak, clinical studies demonstrated that the endogenous growth hormone/IGF-1 excess is associated with cardiovascular implications. Previously, we demonstrated that human peripheral blood lymphocytes represent a suitable system to identify a gene signature, related to dihydrotestosterone or IGF-1 abuse, independent from the type of sport. In addition, in a proteomic study, we demonstrated that dihydrotestosterone 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 peripheral blood lymphocytes could be more prone to transendothelial migration.