The activity of satellite cells and myonuclei during 8 weeks of strength training in young men with suppressed testosterone.

Abstract

Mitigating the effects of skeletal muscle wasting and sarcopenia has numerous clinical applications such as during immobilization, various disease states and healthy ageing. Currently, the best non-pharmacological intervention to alleviate the effects of skeletal muscle loss is resistance training. In this regard, much research has been published examining the effects of resistance exercise and chronic resistance training on pathways that influence skeletal muscle anabolism (Roberts et al. 2010, 2011), catabolism (Dalbo et al. 2011a,b), number of myonuclei (Hanssen et al. 2013), hypertrophy (Krieger 2010) and strength (Naclerio et al. 2013). However, much less is known about the effects of resistance training in the presence of suppressed testosterone which is a topic of great clinical significance. Examining the effects of resistance training in individuals with suppressed testosterone may best be highlighted in patients with cancer who are administered testosterone suppressing pharmaceuticals and the ageing population. There is a clear link between testosterone and skeletal muscle mass and strength, a phenomena embraced by athletes who abuse testosterone and the scientific community. In this regard, a landmark study by Bhasin et al. (2001) reported a positive, dose–response relationship between the administration of testosterone enanthate and fat free mass, strength, power and muscle volume independent of exercise. Given the positive effects of testosterone on skeletal muscle mass and strength, Kvorning (Kvorning et al. 2006) collected data on a group of 22 college-aged, eugonadal males. Participants were randomly assigned to a placebo (n = 10) or goserelin (n = 12) group. Goserelin suppresses testicular production of testosterone through inhibition of pituitary-secreted luteinizing hormone (Cockshott 2000). Drug administration occurred in a double-blind fashion for 12 weeks. Following 4 weeks of drug administration, all participants began an 8 week, full body, resistance training programme. Muscle biopsies were obtained from the vastus lateralis following 4 weeks of drug administration but prior to resistance training and following 8 weeks of resistance training at 4 and 24 h post-exercise. Collected data resulted in a series of published research that reported on the effects of testosterone suppression and resistance training on skeletal muscle mass (Kvorning et al. 2006) and the mRNA expression of androgen receptor, myostatin and genes that influence satellite cell activity (Kvorning et al. 2007). Results from Kvorning et al. (2006) demonstrated the hypertrophic response resulting from resistance training was blunted by testosterone suppression as the goserelin group experienced significantly less muscle hypertrophy than the placebo group (Kvorning et al. 2006). As testosterone has been linked with satellite cell activation and proliferation (Sinha-Hikim et al. 2003), myonuclear number (Kadi 2008) and muscle fibre size (Kadi 2008) Kvorning et al. (2007) used their data to examine the effects of testosterone suppression on genes known to influence satellite cell activity. Interestingly, there were no reported between group differences in the mRNA expression in any of the examined genes (MyoD, myogenin, IGF-1Ea, IGF-1Eb and IGF-1Ec) suggesting endogenous testosterone is not directly involved with the mRNA expression of genes indicative of satellite cell activity during the course of strength training induced skeletal muscle hypertrophy (Kvorning et al. 2007). The results from a study published in this issue of Acta Physiologica by Kvorning et al. (2014) using the same data set from previous investigations (Kvorning et al. 2006, 2007) reported on the effects of testosterone suppression in the presence of resistance training on satellite cell and myonuclear number in type I and type II skeletal muscle fibres. The authors reported there were no within or between group differences in satellite cell or myonuclear number in type I fibres. However, in type II fibres, there was a significant increase in satellite cell content in both groups, but only the placebo group experienced a significant increase in myonuclear number. These findings suggest the short-term suppression of testosterone has no effect on satellite cell proliferation resulting from resistance training. Conversely, testosterone suppression blunts the hypertrophic response of resistance training (Kvorning et al. 2006) and myonuclear number. These novel findings provide evidence suggesting the short-term suppression of testosterone production reduces the skeletal muscle hypertrophic response from resistance training, likely by influencing satellite cell differentiation and/or fusion to post-mitotic fibres. Notwithstanding, it is important to note that resistance training has been shown to stimulate skeletal muscle hypertrophy and increase muscle strength in older males (Kraemer et al. 1999, Verdijk et al. 2009) who presumably present lower circulating testosterone levels. Furthermore, others have experimentally challenged if circulating hormones affect the post-exercise intramuscular anabolic milieu (Wilkinson et al. 2006, West et al. 2009, Mitchell et al. 2013). Thus, there are resistance exercise-induced skeletal muscle adaptations that occur independent of the testosterone–skeletal muscle signalling phenomena. Further investigation into the effects of testosterone suppression (i.e. cancer patients) and reduced endogenous testosterone (i.e. ageing males) on skeletal muscle structure, mass, strength and molecular signalling pathways is warranted. Specifically, future research should examine possible signalling mechanisms that may influence satellite cell differentiation in the presence of diminished testosterone. Clearly, these types of studies have important clinical applications and may offer insights on how to best preserve skeletal muscle during ageing and various disease states. No conflict of interests arose in the completion of our editorial and no external financial support was sought for our work.