Nandrolone decreases mu opioid receptor expression in SH-SY5Y human neuroblastoma cells.
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.
Guarino
Goffredo
G
Department of Pharmacology, University of Bologna, Bologna, Italy.
Spampinato
Santi
S
D000726:Androgen Antagonists / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003609:Dactinomycin / Q000494:pharmacology; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009277:Nandrolone / Q000494:pharmacology*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D000726:Androgen Antagonists; D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D011993:Recombinant Fusion Proteins; D003609:Dactinomycin; C014290:hydroxyflutamide; D009277:Nandrolone; D005485:Flutamide; D008156:Luciferases