Myoanabolic steroids and selective androgen receptor modulators: mechanism of action and perspectives

Abstract

Interest in anabolic steroids has been renewed in the last decade with the discovery of tissue-selective androgen receptor modulators exhibiting high myotropic and small androgenic activity. An explanation put forward by us in 1982 for the mechanism of the preferential myotropic effect of nandrolone (19-nortestosterone) exploits the fundamental difference between the 5α-reductase concentrations in skeletal muscle and androgenic target tissue. In androgenic tissue, testosterone is converted to the more potent 5α-dihydrotestosterone whereas nandrolone is converted to a less potent derivative. As 5α-reduction is negligible in skeletal muscle, this explains why nandrolone shows a greater myotropic to androgenic ratio when compared with testosterone. Anabolic steroids that do not undergo 5α-reduction exert myotropic-androgenic dissociation because their effect in androgenic tissues is not amplified by 5α-reduction. Tissue selectivity by receptor modulators may be achieved by inducing specific conformational changes of the androgen receptor that affect its interaction with transcriptional coregulators. Anabolic activity is mediated by the stimulation of ribosomal RNA synthesis therefore regulation of this synthesis by anabolic steroids would deserve detailed studies.