Testosterone action on skeletal muscle

Abstract

To highlight recent data demonstrating direct anabolic effects of androgens on the mammalian skeletal muscle and review the mechanisms by which testosterone regulates body composition. Testosterone increases lean body mass and decreases fat mass in young men; the magnitude of the changes induced by testosterone in lean and fat mass are correlated with testosterone dose and the prevalent testosterone concentrations. Older men are as responsive to the anabolic effects of testosterone on the muscle as young men, but have increased frequency of adverse events with higher testosterone doses. This reciprocal change in lean and fat mass induced by androgens is best explained by the hypothesis that androgens promote the commitment of mesenchymal pluripotent cells into myogenic lineage and inhibit adipogenesis through an androgen receptor mediated pathway. Resident muscle satellite cells increase in number with testosterone administration forming myoblasts leading to greater numbers of myonuclei in larger myofibers. Testosterone administration is associated with increased size of motor neurons. The roles of 5-alpha reduction and aromatization of testosterone into dihydrotestosterone and estradiol, respectively, in mediating testosterone effects on body composition are poorly understood. Testosterone induces skeletal muscle hypertrophy by multiple mechanisms, including its effects in modulating the commitment of pluripotent mesenchymal cells. These changes in skeletal muscle lead to improved muscle strength and leg power; however, further studies are needed to determine the effects of testosterone on physical function and health-related outcomes in sarcopenia associated with aging and chronic illness.