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.
| Identifer | oai:union.ndltd.org:unibo.it/oai:amsdottorato.cib.unibo.it:693 |
| Date | 06 June 2008 |
| Creators | Guarino, Goffredo <1979> |
| Contributors | Spampinato, Santi Mario |
| Publisher | Alma Mater Studiorum - Università di Bologna |
| Source Sets | Università di Bologna |
| Language | English |
| Detected Language | English |
| Type | Doctoral Thesis, PeerReviewed |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
Page generated in 0.0014 seconds