Cellular and molecular mechanisms responsible for the action of testosterone on human skeletal muscle. A basis for illegal performance enhancement

Abstract

The popularity of testosterone among drug users is due to its powerful effects on muscle strength and mass. Important mechanisms behind the myotrophic effects of testosterone were uncovered both in athletes using steroids for several years and in short-term controlled studies. Both long-term and short-term steroid usage accentuates the degree of fibre hypertrophy in human skeletal muscle by enhancing protein synthesis. A mechanism by which testosterone facilitates the hypertrophy of muscle fibres is the activation of satellite cells and the promotion of myonuclear accretion when existing myonuclei become unable to sustain further enhancement of protein synthesis. Interestingly, long-term steroid usage also enhances the frequency of fibres with centrally located myonuclei, which implies the occurrence of a high regenerative activity. Under the action of testosterone, some daughter cells generated by satellite cell proliferation may escape differentiation and return to quiescence, which help to replenish the satellite cell reserve pool. However, whether long-term steroid usage induces adverse effects of satellite cells remains unknown. Testosterone might also favour the commitment of pluripotent precursor cells into myotubes and inhibit adipogenic differentiation. The effects of testosterone on skeletal muscle are thought to be mediated via androgen receptors expressed in myonuclei and satellite cells. Some evidence also suggests the existence of an androgen-receptorindependent pathway. Clearly, testosterone abuse is associated with an intense recruitment of multiple myogenic pathways. This provides an unfair advantage over non-drug users. The long-term consequences on the regenerative capacity of skeletal muscle are unknown.

Short‐term resource allocation during extensive athletic competition

“…In humans, muscle mass provides one such signal (Griggs et al, 1989; Kadi, 2008). Muscularity provides benefits in sexual selection from both inter‐ and intra‐sexual perspectives (Bribiescas, 2001; Dijkstra & Buunk, 2002; Frederick & Haselton, 2007; Gallup, White, & Gallup, 2007; Lavrakas, 1975).…”

Muscle-specific androgen receptor deletion shows limited actions in myoblasts but not in myofibers in different muscles in vivo

“…The primary cellular targets of androgen action in skeletal muscle remain unresolved (Kadi 2008). Different studies have suggested that androgens act on satellite cells or myoblasts to increase the number of myonuclei (Mulvaney et al 1988, Joubert et al 1994, Joubert & Tobin 1995 or act on myofibers to increase protein content (Sheffield-Moore et al 1999, Ferrando et al 2002, Chen et al 2008, Ophoff et al 2009b.…”

Influence of Mesterolone on Satellite Cell Distribution and Fiber Morphology within Maturing Chicken Pectoralis Muscle

“…While each bird in the previous study of nandrolone received a total of 120 mg nandrolone decanoate injected over a period of 4 weeks, each chicken in this study received a total dose of only about 21 mg mesterolone over the same period of time. One of the suggested mechanisms by which AASs induce muscle hypertrophy is increasing the population of myonuclear androgen receptors upon which they can act (Sinha-Hikim et al, 2004;Kadi, 2008). The activated androgen receptors then bind to selective genes within the myonucleus to increase their rates of transcription (Kadi, 2008).…”

“…One of the suggested mechanisms by which AASs induce muscle hypertrophy is increasing the population of myonuclear androgen receptors upon which they can act (Sinha-Hikim et al, 2004;Kadi, 2008). The activated androgen receptors then bind to selective genes within the myonucleus to increase their rates of transcription (Kadi, 2008). We speculate that the higher dose of nandrolone decanoate led to a greater transcriptional activity of myonuclei, which in turn resulted in a larger MD.…”