title: 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.
authors.affiliation: DSMB, University of Naples "Parthenope,", Naples, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Spaziani
authors.forename: Esther
authors.initials: E
authors.lastname: Imperlini
authors.forename: Annamaria
authors.initials: A
authors.lastname: Mancini
authors.forename: Marianna
authors.initials: M
authors.lastname: Caterino
authors.forename: Pasqualina
authors.initials: P
authors.lastname: Buono
authors.forename: Stefania
authors.initials: S
authors.lastname: Orrù
mesh_terms: D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D058573:Performance-Enhancing Substances / Q000009:adverse effects / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects
chemical_list: D058573:Performance-Enhancing Substances; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: 2D DIGE; Cell biology; IGF-1; IGF-1 receptor; Lymphocytes; Peptide hormone