title: Synergistic effect of DHT and IGF-1 hyperstimulation in human peripheral blood lymphocytes.
abstract: The abuse of mixed or combined performance-enhancing drugs is widespread among athletes and amateurs, adults and adolescents. Clinical studies demonstrated that misuse of these doping agents is associated with serious adverse effects to many organs in human. Previously, we demonstrated in human peripheral blood lymphocytes that high doses of anabolic androgenic steroids, such as dihydrotestosterone (DHT) and growth factors, such as insulin-like growth factor-1 (IGF-1), have effects at gene and protein levels. Supraphysiological treatments of DHT and IGF-1 affected the expression of genes involved in skeletal muscle disorders as well as in cell-mediated immunological response. At protein level, DHT hyperdosage affects cell motility and apoptosis; IGF-1 hyperstimulation triggers an active cytoskeletal reorganization and an overproduction of immune response- and inflammation-related cytokines. In this study, we investigate the combined effects of DHT and IGF-1 hyperdosage in peripheral blood lymphocytes using a differential proteomic approach. DHT and IGF-1 combined treatment affects cell adhesion, migration, and survival through modulation of expression levels of cytokines and paxillin-signaling-related proteins, and activation of several pathways downstream focal adhesion kinase. Our results indicate a synergistic effect of DHT and IGF-1 which has potential implications for health risk factors.
authors: Fondazione IRCCS SDN, Naples, Italy.
authors: Esther
authors: E
authors: Imperlini
authors: DSMB, University of Naples "Parthenope,", Naples, Italy.
authors: Sara
authors: S
authors: Spaziani
authors: DSMB, University of Naples "Parthenope,", Naples, Italy.|CEINGE Biotecnologie Avanzate scarl, Naples, Italy.
authors: Annamaria
authors: A
authors: Mancini
authors: Fondazione IRCCS SDN, Naples, Italy.
authors: Marianna
authors: M
authors: Caterino
authors: Fondazione IRCCS SDN, Naples, Italy.|DSMB, University of Naples "Parthenope,", Naples, Italy.
authors: Pasqualina
authors: P
authors: Buono
authors: Fondazione IRCCS SDN, Naples, Italy.|DSMB, University of Naples "Parthenope,", Naples, Italy.
authors: Stefania
authors: S
authors: Orrù
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011506:Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D011506:Proteins; D013196:Dihydrotestosterone; D007334:Insulin-Like Growth Factor I; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D053148:Caspase 3
keywords: 2D DIGE; AR; Cell biology; DHT; IGF-1; IGF1R