The differential hormonal milieu of morning versus evening, may have an impact on muscle hypertrophic potential

Substantial gains in muscle strength and hypertrophy are clearly associated with the routine performance of resistance training. What is less evident is the optimal timing of the resistance training stimulus to elicit these significant functional and structural skeletal muscle changes. Therefore, this investigation determined the impact of a single bout of resistance training performed either in the morning or evening upon acute anabolic signalling (insulin-like growth factor-binding protein-3 (IGFBP-3), myogenic index and differentiation) and catabolic processes (cortisol). Twenty-four male participants (age 21.4±1.9yrs, mass 83.7±13.7kg) with no sustained resistance training experience were allocated to a resistance exercise group (REP). Sixteen of the 24 participants were randomly selected to perform an additional non-exercising control group (CP) protocol. REP performed two bouts of resistance exercise (80% 1RM) in the morning (AM: 0800 hrs) and evening (PM: 1800 hrs), with the sessions separated by a minimum of 72 hours. Venous blood was collected immediately prior to, and 5 min after, each resistance exercise and control sessions. Serum cortisol and IGFBP-3 levels, myogenic index, myotube width, were determined at each sampling period. All data are reported as mean ± SEM, statistical significance was set at P≤0.05. As expected a significant reduction in evening cortisol concentration was observed at pre (AM: 98.4±10.5, PM: 49.8±4.4 ng/ml, P0.05). Timing of resistance training regimen in the evening appears to augment some markers of hypertrophic potential, with elevated IGFBP-3, suppressed cortisol and a superior cellular environment. Further investigation, to further elucidate the time course of peak anabolic signalling in morning vs evening training conditions, are timely

Molecular networks of human muscle adaptation to exercise and age

Physical activity and molecular ageing presumably interact to precipitate musculoskeletal decline in humans with age. Herein, we have delineated molecular networks for these two major components of sarcopenic risk using multiple independent clinical cohorts. We generated genome-wide transcript profiles from individuals (n = 44) who then undertook 20 weeks of supervised resistance-exercise training (RET). Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%), and when applying Ingenuity Pathway Analysis (IPA) up-stream analysis to ~580 genes that co-varied with gain in lean mass, we identified rapamycin (mTOR) signaling associating with growth (P = 1.4×10−30). Paradoxically, those displaying most hypertrophy exhibited an inhibited mTOR activation signature, including the striking down-regulation of 70 rRNAs. Differential analysis found networks mimicking developmental processes (activated all-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6×10−13) and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = −2.3; P = 3×10−7)) with RET. Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise training (EET), they appear to represent “generic” physical activity responsive gene-networks. For age, we found that differential gene-expression methods do not produce consistent molecular differences between young versus old individuals. Instead, utilizing two independent cohorts (n = 45 and n = 52), with a continuum of subject ages (18–78 y), the first reproducible set of age-related transcripts in human muscle was identified. This analysis identified ~500 genes highly enriched in post-transcriptional processes (P = 1×10−6) and with negligible links to the aforementioned generic exercise regulated gene-sets and some overlap with ribosomal genes. The RNA signatures from multiple compounds all targeting serotonin, DNA topoisomerase antagonism, and RXR activation were significantly related to the muscle age-related genes. Finally, a number of specific chromosomal loci, including 1q12 and 13q21, contributed by more than chance to the age-related gene list (P = 0.01–0.005), implying possible epigenetic events. We conclude that human muscle age-related molecular processes appear distinct from the processes regulated by those of physical activity

The exercise-induced biochemical milieu enhances collagen content and tensile strength of engineered ligaments

KEY POINTS: Exercise acutely increases the concentrations of metabolites and hormones such as growth hormone (GH) and, to a lesser extent, insulin‐like growth factor 1 (IGF‐1); however, the biological function of this response is unclear. Pharmacological administration of these hormones stimulates collagen synthesis in muscle and tendon; however, whether the post‐exercise biochemical milieu has a similar action is unknown. Treating engineered ligaments with serum obtained from young healthy men after exercise resulted in more collagen and improved tensile strength over those treated with serum from resting men. Further, we show that the increase in collagen induced by post‐exercise serum (i) is not reproduced by treatment with recombinant GH or IGF‐1, and (ii) is associated with the activation of PI3 kinase/mTORC1 and ERK1/2 signalling. ABSTRACT: Exercise stimulates a dramatic change in the concentration of circulating hormones, such as growth hormone (GH), but the biological functions of this response are unclear. Pharmacological GH administration stimulates collagen synthesis; however, whether the post‐exercise systemic milieu has a similar action is unknown. We aimed to determine whether the collagen content and tensile strength of tissue‐engineered ligaments is enhanced by serum obtained post‐exercise. Primary cells from a human anterior cruciate ligament (ACL) were used to engineer ligament constructs in vitro. Blood obtained from 12 healthy young men 15 min after resistance exercise contained GH concentrations that were ∼7‐fold greater than resting serum (P < 0.001), whereas IGF‐1 was not elevated at this time point (P = 0.21 vs. rest). Ligament constructs were treated for 7 days with medium supplemented with serum obtained at rest (RestTx) or 15 min post‐exercise (ExTx), before tensile testing and collagen content analysis. Compared with RestTx, ExTx enhanced collagen content (+19%; 181 ± 33 vs. 215 ± 40 μg per construct P = 0.001) and ligament mechanical properties – maximal tensile load (+17%, P = 0.03 vs. RestTx) and ultimate tensile strength (+10%, P = 0.15 vs. RestTx). In a separate set of engineered ligaments, recombinant IGF‐1, but not GH, enhanced collagen content and mechanics. Bioassays in 2D culture revealed that acute treatment with post‐exercise serum activated mTORC1 and ERK1/2. In conclusion, the post‐exercise biochemical milieu, but not recombinant GH, enhances collagen content and tensile strength of engineered ligaments, in association with mTORC1 and ERK1/2 activation

Attenuation of Resting but Not Load-Mediated Protein Synthesis in Prostate Cancer Patients on Androgen Deprivation

Context: Androgen deprivation therapy (ADT) is a common prostate cancer (PCa) treatment but results in muscular atrophy. Periodic increases in muscle protein synthesis (MPS) that occur after resistance exercise or protein intake may ameliorate this muscle loss, but the impact of these anabolic stimuli during ADT is unclear. Objective: To determine the acute MPS response to whey protein supplementation with and without resistance exercise during ADT. Design: Acute response in PCa patients vs age-matched controls (CON). Setting: Academic laboratory setting. Participants: PCa patients on ADT (N = 8) and CON (N = 10). Intervention: A standardized diet was consumed for 2 days prior to performing unilateral knee extension resistance exercise followed by ingestion of 40 g of whey protein. Main Outcome Measures: Bilateral biopsies and stable isotope infusions were used to determine MPS rates at rest after protein ingestion with and without resistance exercise. Results: Baseline MPS during ADT was suppressed relative to CON (P = 0.01). Protein consumption stimulated MPS in both groups (approximate twofold increase, both P < 0.001), but to a greater extent in CON (P = 0.003). Protein plus resistance exercise increased MPS (∼3.4-fold increase, both P < 0.001) to a greater extent than did protein alone (P < 0.001), but with no difference between groups (P = 0.380). Conclusions: ADT reduces basal and protein feeding-induced rises in MPS; however, combined protein ingestion with resistance exercise stimulated MPS to a similar degree as CON. Testosterone appears to play a role in maintaining muscle mass but is not necessary to initiate a robust response in MPS following resistance exercise when combined with protein ingestion

Role of Testosterone on Muscle Protein Syntheis during Prostate Cancer Treatment

Abstract for paper: Medicine and science in sports and exercise Volume 48(5S) Supplement 1, May 2016, p 358–359 DOI 10.1249/01.mss.0000486086.07429.4

Exercise-induced responses in salivary testosterone, cortisol, and their ratios in men:a meta-analysis

Background: Testosterone, cortisol and their ratios may be indicators of anabolic status, but technical issues surrounding blood sampling has limited wider application. The advent of salivary testosterone (sal-T) analysis simplified sample acquisition, resulting in a subsequent rapid increase in the number of published research articles. Objective: The objective of this study was to undertake a meta-analysis to determine the effect of acute exercise bouts on post exercise sal-T and salivary cortisol (sal-C) concentrations and their ratio (sal-T:C). Data Sources: Relevant databases such as PubMed, Web of Science, Science Direct and SPORTDiscus were searched up to and including 31 December 2013 for the term ‘saliva AND testosterone AND exercise’. Study Selection: Studies (n = 21) selected from the 933 identified included randomised controlled trials (RCTs; n = 2), uncontrolled trials (UCTs; n = 18) and control trials (CTs; n = 1), all of which had an exercise component characterised as either aerobic, resistance or power training, each with acute sal-T and sal-C measurement obtained within 30 min of exercise bout completion. Study Appraisal and Synthesis Methods: A meta-analysis was conducted on change in sal-T, sal-C and the sal-T:C ratio following exercise using standard difference in means (SDM) and a random effects model. Results: For aerobic, resistance and power exercise, the overall SDMs for sal-T were 0.891, 1.061 and 0.509, respectively; for sal-C, the SDMs were 3.041, 0.773 and 1.200, respectively. For sal-T:C, the SDMs were -2.014, 0.027 and -0.968, respectively. RCTs, UCTs and CTs were separated by subgroup analysis. There were significant differences in overall weighted SDM values for sal-T between RCTs, UCTs and CTs within exercise modes. When examining aerobic exercise interventions, a quantitative interaction of study design was observed. RCTs resulted in a greater SDM than UCTs (1.337 vs. 0.446). Power interventions displayed a qualitative interaction with study design. UCTs where baseline measures were obtained 24 h before exercise had an SDM of –1.128, whereas UCTs where baseline was determined immediately prior to exercise had an SDM of 0.486. The single CT trial had an SDM of 2.260. Resistance exercise interventions were primarily UCTs; however, an observed influence of baseline sampling time whereby immediately preand 24 h pre-exercise resulted in differing SDMs. The sole resistance exercise RCTs resulted in the greatest SDM (2.500). Conclusion: The current body of evidence regarding acute responses of sal-T to exercise is weak. This meta-analysis identifies varying exercise-dependent effect sizes. Each appear to be greatly influenced by study design and sample timing. There is a need for more RCTs and a standardised methodology for the measurement of salivary hormones in order to better determine the effect of exercise modality