Androgen receptor signaling induced by supraphysiological doses of dihydrotestosterone in human peripheral blood lymphocytes

Esther Imperlini, Annamaria Mancini, Sara Spaziani, Domenico Martone, Andreina Alfieri, Marica Gemei, Luigi Del Vecchio, Pasqualina Buono, Stefania Orrù

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)3165-3175
Number of pages11
JournalProteomics
Volume10
Issue number17
DOIs
Publication statusPublished - Sep 2010

Keywords

  • 2-D DIGE
  • Androgen receptor
  • Cell biology
  • Dihydrotestosterone
  • Lymphocytes
  • Steroids abuse

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

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