DIFFERENT PATTERNS OF METABOLISM DETERMINE THE RELATIVE ANABOLIC ACTIVITY OF 19-NORANDROGENS

Testosterone, the principal androgen secreted by Leydig cells, exerts a wide range of actions including growth of the male reproductive trac t (androgenic effects) and growth of non-reproductive tissues such as muscle, kidney, liver, and salivary gland (anabolic effects). As andro genic steroids were discovered some were found to have relatively more anabolic than androgenic activity. The results reviewed in this repor t suggest that these differences result, in part, from the differentia l metabolism of the steroids in individual tissues and the varied acti vities 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-nortestoste rone (NT) is 5 alpha-reduced, its affinity for AR decreases, resulting in a decrease in its androgenic potency. However, their anabolic pote ncy remains unchanged since significant 5 alpha-reduction of the stero ids does not occur in the muscle. 7 alpha-methyl-19-nortestosterone (M ENT) does not get 5 alpha-reduced due to steric hindrance from the 7 a lpha-methyl group. Therefore, the androgenic potency of MENT is not am plified as happens with testosterone. These metabolic differences are responsible for the increased anabolic activity of NT and MENT compare d 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 b y human placental and rat ovarian aromatase suggests that some of the anabolic actions of MENT may be mediated by this estrogen.