Testosterone supplementation upregulates androgen receptor expression and translational capacity during severe energy deficit

Abstract

Testosterone supplementation during energy deficit promotes whole-body lean mass accretion, but the mechanisms underlying that effect remain unclear. To elucidate those mechanisms, skeletal muscle molecular adaptations were assessed from muscle biopsies collected before (Resting), 1 h (Post) and 6 h (Recovery) after exercise and a mixed meal (40 g protein, 1 h post-exercise) following 14 days of weight maintenance (WM) and 28 days of an exercise- and diet-induced 55% energy deficit (ED) in 50 physically active, non-obese men treated with 200 mg testosterone enanthate/week (TEST) or placebo (PLA) during the ED. Participants (n=10/group) exhibiting substantial increases (TEST) in leg lean mass and total testosterone were compared to those exhibiting decreases in both of these measures (PLA). Resting androgen receptor (AR) protein content was higher and fibroblast growth factor-inducible 14 (Fn14), IL-6 receptor (IL-6R), and muscle ring-finger protein-1 (MuRF1) gene expression were lower in TEST versus PLA during ED relative to WM (P < 0.05). Changes in inflammatory, myogenic, and proteolytic gene expression did not differ between groups after exercise and recovery feeding. Mechanistic target of rapamycin (mTOR) signaling (i.e., translational efficiency) was also similar between groups at rest and after exercise and the mixed meal. Muscle total RNA content (i.e., translational capacity) increased more during ED in TEST than PLA (P < 0.05). These findings indicate that attenuated proteolysis at rest, possibly downstream of AR, Fn14, and IL-6R signaling, and increased translational capacity, not efficiency, may drive lean mass accretion with testosterone administration during energy deficit.

Lean mass sparing in resistance-trained athletes during caloric restriction: the role of resistance training volume

“…Without any counteracting stimuli (e.g., RT), attenuation of MPS ultimately leads to a negative net protein balance and, hence, to lean tissue loss (Roth et al 2021;Pasiakos et al 2013). This is supported by the data of athletes taking performance-enhancing drugs who, due to ergogenic effects on protein turnover, do not show significant lean tissue loss (Pasiakos et al 2019;de Souza et al 2018;Howard et al 2020). Although RT is widely recognized as a potent countermeasure against CR-induced alterations, lean tissue loss is also often reported (Weinheimer et al 2010).…”

Exposure to sevoflurane results in changes of transcription factor occupancy in sperm and inheritance of autism

“…Ar interacts with DNA when it is bound by androgens such as testosterone [69, 70], and it has also been shown that testosterone levels are positively correlated with Ar gene expression [71]. Supplements of testosterone increase Ar gene expression in human studies [72, 73]. These observations are interesting in the context of published evidence showing that exposure to sevoflurane increases testosterone levels in male animals [74, 75] and that a surge of testosterone takes place during germ cell and gonadal sex differentiation [70].…”

Molecular Regulators of Muscle Mass and Mitochondrial Remodeling Are Not Influenced by Testosterone Administration in Young Women

“…ARs are not only responsible for mediating the anabolic effects of T ( 10 , 36 ), but are also critical for muscle fiber remodeling following chronic RT ( 37 , 38 ). In males, administration of T is commonly accompanied by increased intramuscular AR content ( 13 , 14 , 17 , 35 , 39 ), but no study has previously examined whether such change occur in young women. In the present study, despite raising T serum concentrations ~ fivefold above basal levels, AR protein expression remained unchanged, a somewhat unexpected finding given that basal muscle AR content is lower in women than in men ( 40 ).…”

“…Studies seeking to depict the role of mTORC1-signaling in human muscle following T provision are scarce and have provided mixed results. Howard et al., 2020 showed that weekly injections of T enanthate (200 mg) during 28-days of severe energy deficit did not alter mTORC1-signaling following exercise and protein intake in young men ( 13 ). On the other hand, Gharahdaghi and colleagues showed that biweekly T injections (Sustanon, 250 mg) in combination with resistance training potentiated exercise-induced mTORC1-signaling in old men ( 14 ).…”