We have recently demonstrated performance-enhancing effects of moderately elevated testosterone concentrations in young women. Here we present novel evidence that testosterone alters muscle morphology in these women, resulting in type II fiber hypertrophy and improved capillarization. Our findings suggest that low doses of testosterone potently impact skeletal muscle after only 10 wk. These data provide unique insights into muscle adaptation and support the performance-enhancing role of testosterone in women on the muscle fiber level.

Human skeletal muscle characteristics such as fiber type composition, fiber size and myonuclear content are widely studied in clinical and sports related contexts. Being aware of the methodological and biological variability of the characteristics is a critical aspect in study design and outcome interpretation, but comprehensive data on the variability of morphological features in human skeletal muscle is currently limited. Accordingly, in the present study, m. vastus lateralis biopsies (10 per subject) from young and healthy individuals, collected in a systematic manner, were analyzed for various characteristics using immunohistochemistry (n=7) and SDS-PAGE (n=25). None of the analyzed parameters; fiber type % (FT%), type I and II CSA (fCSA), percentage fiber type area (fCSA%), myosin heavy chain composition (MyHC%), type IIX content, myonuclear content or myonuclear domain varied in a systematic manner longitudinally along the muscle or between the two legs. The average within subject coefficient of variation for FT%, fCSA, fCSA%, and MyHC% ranged between 13-18%, but was only 5% for fiber specific myonuclear content, which reduced the variability for myonuclear domain size to 11-12%. Pure type IIX fibers and type IIX MyHC were randomly distributed and present in <24% of the analyzed samples, with the average content being 0.1 and 1.1%, respectively. In conclusion, leg or longitudinal orientation does not seem to be an important aspect to consider when investigating human vastus lateralis characteristics. However, single muscle biopsies should preferably not be used when studying fiber type and fiber size related aspects given the notable sample to sample variability.

Human skeletal muscle is a dynamic and highly plastic tissue, capable of altering its phenotype in response to divergent stimuli, such as chronic exercise or disuse. 1 The adaptability of muscle is in turn influenced by a number of different factors, such as sex, 2 age, 3 training history, 4 and fiber type composition. 5 Categorized according to myosin heavy chain

Aim: Hypoxia has been shown to reduce resistance exercise-induced stimulation of protein synthesis and long-term gains in muscle mass. However, the mechanism whereby hypoxia exerts its effect is not clear. Here, we examine the effect of acute hypoxia on the activity of several signalling pathways involved in the regulation of muscle growth following a bout of resistance exercise.Methods: Eight men performed two sessions of leg resistance exercise in normoxia or hypoxia (12% O 2 ) in a randomized crossover fashion. Muscle biopsies were obtained at rest and 0, 90,180 minutes after exercise. Muscle analyses included levels of signalling proteins and metabolites associated with energy turnover.Results: Exercise during normoxia induced a 5-10-fold increase of S6K1 Thr389 phosphorylation throughout the recovery period, but hypoxia blunted the increases by ~50%. Phosphorylation of JNK Thr183/Tyr185 and the JNK target SMAD2 Ser245/250/255 was increased by 30-to 40-fold immediately after the exercise in normoxia, but hypoxia blocked almost 70% of the activation. Throughout recovery, phosphorylation of JNK and SMAD2 remained elevated following the exercise in normoxia, but the effect of hypoxia was lost at 90-180 minutes postexercise. Hypoxia had no effect on exercise-induced Hippo or autophagy signalling and ubiquitin-proteasome related protein levels. Nor did hypoxia alter the changes induced by exercise in high-energy phosphates, glucose 6-P, lactate or phosphorylation of AMPK or ACC. Conclusion:We conclude that acute severe hypoxia inhibits resistance exerciseinduced mTORC1-and JNK signalling in human skeletal muscle, effects that do not appear to be mediated by changes in the degree of metabolic stress in the muscle.

Blood flow restriction (BFR) with low-load resistance exercise (RE) is often used as a surrogate to traditional high-load RE to stimulate muscular adaptations, such as hypertrophy and strength. However, it is not clear whether such adaptations are achieved through similar cellular and molecular processes. We compared changes in muscle function, morphology and signaling pathways between these differing training protocols. Twenty-one males and females (mean ± SD: 24.3 ± 3.1 years) experienced with resistance training (4.9 ± 2.6 years) performed nine weeks of resistance training (three times per week) with either high-loads (75-80% 1RM; HL-RT), or low-loads with BFR (30-40% 1RM; LL-BFR). Before and after the training intervention, resting muscle biopsies were collected, and quadricep cross-sectional area (CSA), muscular strength and power were measured. Approximately 5 days following the intervention, the same individuals performed an additional 'acute' exercise session under the same conditions, and serial muscle biopsies were collected to assess hypertrophic- and ribosomal-based signaling stimuli. Quadricep CSA increased with both LL-BFR (7.4±4.3%) and HL-RT (4.6±2.9%), with no significant differences between training groups (p=0.37). Muscular strength also increased in both training groups, but with superior gains in squat 1RM occurring with HL-RT (p<0.01). Acute phosphorylation of several key proteins involved in hypertrophy signaling pathways, and expression of ribosomal RNA transcription factors occurred to a similar degree with LL-BFR and HL-RT (all p>0.05 for between-group comparisons). Together, these findings validate low-load resistance training with continuous BFR as an effective alternative to traditional high-load resistance training for increasing muscle hypertrophy in trained individuals.