Nandrolone and other anabolic androgenic steroids (AAS) can alter the expression and function of neurotransmitter systems. These effects can help to explain the behavioral changes, drug dependence and neurodegeneration observed in steroid abusers. Nandrolone (10-8M–10-5M) causes a time- and concentration-dependent downregulation of mu opioid receptor (MOR) transcripts in SH-SY5Y neuroblastoma cells. This effect is prevented by the androgen receptor (AR) antagonist hydroxyflutamide. Receptor binding assays confirmed a decrease in MOR of approximately 40% in nandrolone treated cells. Treatment with actinomycin D (10-5M), a transcription inhibitor, revealed that nandrolone mainly regulates MOR mRNA stability. In cells transfected with a human MOR luciferase promoter/reporter construct, nandrolone does not alter the rate of gene transcription. Conversely, it reduces delta opioid receptor (DOR) mRNA and the number of DOR binding sites in the neuronal hybrid cells NG 108-15 partly decreasing the rate of transcription of DOR mRNA: an effect insensitive to hydroxyflutamide. These results suggest that AAS may downregulate MOR and DOR expression through different transcriptional and post-transcriptional actions.
Genomic and non-genomic effects of anabolic steroids on opioid receptor gene expression in neuronal cells
BEDINI, ANDREA;BAIULA, MONICA;SPAMPINATO, SANTI MARIO
2010
Abstract
Nandrolone and other anabolic androgenic steroids (AAS) can alter the expression and function of neurotransmitter systems. These effects can help to explain the behavioral changes, drug dependence and neurodegeneration observed in steroid abusers. Nandrolone (10-8M–10-5M) causes a time- and concentration-dependent downregulation of mu opioid receptor (MOR) transcripts in SH-SY5Y neuroblastoma cells. This effect is prevented by the androgen receptor (AR) antagonist hydroxyflutamide. Receptor binding assays confirmed a decrease in MOR of approximately 40% in nandrolone treated cells. Treatment with actinomycin D (10-5M), a transcription inhibitor, revealed that nandrolone mainly regulates MOR mRNA stability. In cells transfected with a human MOR luciferase promoter/reporter construct, nandrolone does not alter the rate of gene transcription. Conversely, it reduces delta opioid receptor (DOR) mRNA and the number of DOR binding sites in the neuronal hybrid cells NG 108-15 partly decreasing the rate of transcription of DOR mRNA: an effect insensitive to hydroxyflutamide. These results suggest that AAS may downregulate MOR and DOR expression through different transcriptional and post-transcriptional actions.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
