title: Androgen receptor signaling induced by supraphysiological doses of dihydrotestosterone in human peripheral blood lymphocytes.
abstract: Anabolic androgenic steroids, a class of steroid hormones related to testosterone, are natural ligands of androgen receptor (AR), a member of the nuclear receptor superfamily of ligand-activated transcription factors. AR binds specific DNA elements, known as androgen-response elements. Testosterone, the main male sexual hormone, binds AR directly and indirectly, through conversion into dihydrotestosterone (DHT), its more active metabolite. Anabolic androgenic steroids are frequently detected in the urine of doped athletes; their consumption is also growing among sport amateurs and adolescents. The effects of androgens can differ depending on the target cells and/or tissues. To gain insight into transcription activation mechanisms of AR, we investigated AR protein signaling in human peripheral blood lymphocytes treated with supraphysiological doses of DHT. We performed a comparative proteomic analysis and we identified about 30 differentially expressed proteins. At least five species contained a consensus androgen-response elements sequence in the promoter region of related coding genes. The analysis also revealed that high doses of DHT activate the drug detoxification process, could stimulate an increase in cell motility and exert a prosurvival effect rather than an apoptotic one.
authors.affiliation: Fondazione SDN-IRCCS, Napoli, Italy.
authors.forename: Esther
authors.initials: E
authors.lastname: Imperlini
authors.forename: Annamaria
authors.initials: A
authors.lastname: Mancini
authors.forename: Sara
authors.initials: S
authors.lastname: Spaziani
authors.forename: Domenico
authors.initials: D
authors.lastname: Martone
authors.forename: Andreina
authors.initials: A
authors.lastname: Alfieri
authors.forename: Marica
authors.initials: M
authors.lastname: Gemei
authors.forename: Luigi
authors.initials: L
authors.lastname: del Vecchio
authors.forename: Pasqualina
authors.initials: P
authors.lastname: Buono
authors.forename: Stefania
authors.initials: S
authors.lastname: Orrù
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D019295:Computational Biology; D013196:Dihydrotestosterone / Q000494:pharmacology*; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020543:Proteome / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D011944:Receptors, Androgen / Q000378:metabolism*; D015203:Reproducibility of Results; D020218:Response Elements; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D020543:Proteome; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D053148:Caspase 3