title: Comparison of the receptor binding properties of nandrolone and testosterone under in vitro and in vivo conditions.
abstract: Previous in vitro binding studies with androgen receptors in rat seminal vesicles (Toth M. and Zakar T., J. steroid Biochem. 17 (1982) 653-660) have shown that the difference in the effects of nandrolone (N) and testosterone (T) is caused by the fact that 5 alpha-reduction increases the affinity of T and decreases the affinity of N. We confirmed this result using androgen receptors in rat prostate and intact human MCF-7 cells. We also analysed the receptor binding properties of N, T, dihydronandrolone (DHN) and dihydrotestosterone (DHT) in vivo following a combined 2-h infusion of a physiological dose of [3H]T and the same dose of [3H]N in castrated male rats, which permitted a direct comparison of the accumulation of [3H]N, [3H]T, [3H]DHN and [3H]DHT in different sub-cellular fractions of various tissues. There was a considerable accumulation of radioactivity in the liver, but no retention of active compounds. In the prostate there was a preferential retention of [3H]DHT over [3H] DHN in the receptor fractions whereas in thymus, spleen and muscular tissues [3H]N and [3H]T were retained in equal amounts. The kidney showed a preferential retention of [3H]N over [3H]T. The present results explain the relatively strong effect of nandrolone compared to that of testosterone on target tissues devoid of 5 alpha-reductase activity (e.g. muscular tissue) compared to its relatively weak effect on tissues with a relatively high 5 alpha-reductase content (e.g. prostate).
mesh_terms: D000818:Animals; D002369:Castration; D002460:Cell Line; D013196:Dihydrotestosterone / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D009277:Nandrolone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D011467:Prostate / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D011944:Receptors, Androgen; D011987:Receptors, Steroid; D013196:Dihydrotestosterone; C037332:5-dihydro-19-nortestosterone; D013739:Testosterone; D009277:Nandrolone