Direct interactions of androgenic/anabolic steroids with the peripheral benzodiazepine receptor in rat brain: implications for the psychological and physiological manifestations of androgenic/anabolic steroid abuse.
The peripheral benzodiazepine receptor (PBR) is a mitochondrial protein involved in regulating steroid synthesis and transport. We report here the effects of androgenic/anabolic steroids (AAS) on the binding of the PBR-specific ligand [3H] PK11195 to male rat brain cortical synaptoneurosomes. Two synthetic AAS, stanozolol and 17beta-testosterone cypionate (17beta-cyp), significantly inhibited 1 nM [3H] PK11195 binding at concentrations greater than 5 and 25 microM, respectively. Stanozolol was the most effective inhibitor, reducing [3H] PK11195 binding by up to 75%, compared to only 40% inhibition by 17beta-cyp, at 50 microM AAS concentration. Two other AAS, 17alpha-methyltestosterone and nortestosterone decanoate, were incapable of inhibiting [3H] PK11195 binding at concentrations up to 50 microM. On the basis of Scatchard/Rosenthal analysis, [3H] PK11195 binds to two classes of binding sites, and the inhibition of [3H] PK11195 binding by stanozolol appears to be allosteric, primarily reducing binding to the higher affinity [3H] PK11195 binding site. These results, in combination with earlier studies indicating the direct effects of AAS on the function of additional central nervous system receptor complexes, suggest that the behavioral and psychological effects of AAS result from the interactions of AAS with multiple regulatory systems in the brain.
Masonis
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Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, U.S.A.
McCarthy
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D045930:Anabolic Agents / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D058785:GABA-A Receptor Agonists; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008777:Methyltestosterone / Q000378:metabolism / Q000494:pharmacology; D009277:Nandrolone / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013197:Stanozolol / Q000378:metabolism / Q000494:pharmacology; D019966:Substance-Related Disorders / Q000209:etiology; D013574:Synaptosomes / Q000378:metabolism*; D013739:Testosterone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
D045930:Anabolic Agents; D058785:GABA-A Receptor Agonists; D007546:Isoquinolines; D011963:Receptors, GABA-A; D013739:Testosterone; D013197:Stanozolol; D009277:Nandrolone; C016131:testosterone 17 beta-cypionate; D008777:Methyltestosterone; C037850:PK 11195