Genomic and non genomic effects of elevated concentration of anabolic steroids in human neuronal cells

Guarino, Goffredo (2008) Genomic and non genomic effects of elevated concentration of anabolic steroids in human neuronal cells, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Biotecnologie cellulari e molecolari, 20 Ciclo. DOI 10.6092/unibo/amsdottorato/693.
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Nandrolone and other anabolic androgenic steroids (AAS) at elevated concentration can alter the expression and function of neurotransmitter systems and contribute to neuronal cell death. This effect can explain the behavioural changes, drug dependence and neuro degeneration observed in steroid abuser. Nandrolone treatment (10-8M–10-5M) caused a time- and concentration-dependent downregulation of mu opioid receptor (MOPr) transcripts in SH-SY5Y human neuroblastoma cells. This effect was prevented by the androgen receptor (AR) antagonist hydroxyflutamide. Receptor binding assays confirmed a decrease in MOPr of approximately 40% in nandrolonetreated cells. Treatment with actinomycin D (10-5M), a transcription inhibitor, revealed that nandrolone may regulate MOPr mRNA stability. In SH-SY5Y cells transfected with a human MOPr luciferase promoter/reporter construct, nandrolone did not alter the rate of gene transcription. These results suggest that nandrolone may regulate MOPr expression through post-transcriptional mechanisms requiring the AR. Cito-toxicity assays demonstrated a time- and concentration dependent decrease of cells viability in SH-SY5Y cells exposed to steroids (10-6M–10-4M). This toxic effects is independent of activation of AR and sigma-2 receptor. An increased of caspase-3 activity was observed in cells treated with Nandrolone 10-6M for 48h. Collectively, these data support the existence of two cellular mechanisms that might explain the neurological syndromes observed in steroids abuser.

Tipologia del documento
Tesi di dottorato
Guarino, Goffredo
Dottorato di ricerca
Settore disciplinare
Settore concorsuale
Parole chiave
mopr nandrolone mrna stability neurotoxicity androgen receptor shsy5y
Data di discussione
6 Giugno 2008

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