Abstract
Nandrolone and other anabolic androgenic steroids alter the expression and function of neurotransmitter systems and contribute to drug dependence. Nandrolone treatment (10-10 M) caused a time-dependent and concentration-dependent downregulation of mu opioid receptor (MOPr) transcripts in SH-SY5Y human neuroblastoma cells. This effect was prevented by the androgen receptor antagonist hydroxyflutamide. Receptor binding assays confirmed a decrease in MOPr of approximately 40% in nandrolone-treated cells. Treatment with actinomycin D (10 (-5)M), a transcription inhibitor, revealed that nandrolone might 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 posttranscriptional mechanisms requiring the androgen receptor.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Androgen Antagonists / pharmacology
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Blotting, Western
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Cell Line, Tumor
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Dactinomycin / pharmacology
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Flutamide / analogs & derivatives
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Flutamide / pharmacology
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Gene Expression Regulation, Neoplastic / drug effects*
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Humans
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Luciferases / genetics
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Luciferases / metabolism
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Nandrolone / pharmacology*
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Neuroblastoma / genetics
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Neuroblastoma / metabolism
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Neuroblastoma / pathology
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Nucleic Acid Synthesis Inhibitors / pharmacology
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Plasmids / genetics
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Promoter Regions, Genetic / genetics
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Opioid, mu / genetics*
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Receptors, Opioid, mu / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Transfection
Substances
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Androgen Antagonists
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Nucleic Acid Synthesis Inhibitors
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RNA, Messenger
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Receptors, Opioid, mu
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Recombinant Fusion Proteins
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Dactinomycin
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hydroxyflutamide
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Nandrolone
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Flutamide
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Luciferases