title: Different patterns of metabolism determine the relative anabolic activity of 19-norandrogens.
abstract: Testosterone, the principal androgen secreted by Leydig cells, exerts a wide range of actions including growth of the male reproductive tract (androgenic effects) and growth of non-reproductive tissues such as muscle, kidney, liver, and salivary gland (anabolic effects). As androgenic steroids were discovered some were found to have relatively more anabolic than androgenic activity. The results reviewed in this report suggest that these differences result, in part, from the differential metabolism of the steroids in individual tissues and the varied activities of the individual metabolites. In the accessory sex organs (e.g. the prostate) testosterone is 5 alpha-reduced to dihydrotestosterone (DHT) which, due to its higher affinity for androgen receptors (AR), amplifies the action of testosterone. In contrast, when 19-nortestosterone (NT) is 5 alpha-reduced, its affinity for AR decreases, resulting in a decrease in its androgenic potency. However, their anabolic potency remains unchanged since significant 5 alpha-reduction of the steroids does not occur in the muscle. 7 alpha-methyl-19-nortestosterone (MENT) does not get 5 alpha-reduced due to steric hindrance from the 7 alpha-methyl group. Therefore, the androgenic potency of MENT is not amplified as happens with testosterone. These metabolic differences are responsible for the increased anabolic activity of NT and MENT compared to testosterone. Part of the biological effects of testosterone are mediated by its aromatization to estrogens. The fact that MENT is also aromatized to 7 alpha-methyl estradiol, a potent estrogen, in vitro by human placental and rat ovarian aromatase suggests that some of the anabolic actions of MENT may be mediated by this estrogen.
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10021, USA.
authors.forename: K
authors.initials: K
authors.lastname: Sundaram
authors.forename: N
authors.initials: N
authors.lastname: Kumar
authors.forename: C
authors.initials: C
authors.lastname: Monder
authors.forename: C W
authors.initials: CW
authors.lastname: Bardin
mesh_terms: D045930:Anabolic Agents / Q000378:metabolism*; D000818:Animals; D042944:Cholestenone 5 alpha-Reductase; D005260:Female; D008099:Liver / Q000378:metabolism; D008297:Male; D009277:Nandrolone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D009919:Orchiectomy; D010053:Ovary / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D051381:Rats; D013739:Testosterone / Q000494:pharmacology
chemical_list: D045930:Anabolic Agents; D013739:Testosterone; C064709:trestolone; D009277:Nandrolone; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase