Response as peak values may not be reached h after gh

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response, as peak values may not be reached between 16-28 h after GH release [20]. Furthermore, low-intensity resistance exercise combined with BFR does not appear to augment the testosterone response [50, 96]. This may be explained by the protocols either being too low in volume or intensity, as a threshold for these variables must be met to elicit a significant testosterone response [20]. Cell Signalling Resistance exercise is associated with a mechanical disruption that is able to activate the mTOR signalling pathway, which plays a significant role in stimulating muscle protein synthesis via translation and initiation [103]. Ribosomal S6 kinase 1 (S6K1) is a key downstream regulator of the mTOR pathway that is involved in the regulation of mRNA translation initiation and, as a result, is critical to enhance muscle protein synthesis and subsequently skeletal muscle hypertrophy [104]. A prominent study by Fujita et al. [50] demonstrated an increase S6K1 phosphorylation following low-intensity BFR exercise at 20% 1RM, in addition to, a significantly greater increase in muscle protein synthesis at 3 h post-exercise, while no change was observed in the control group. Similarly, Fry et al. [105] reported a significant increase in both S6K1 phosphorylation and muscle protein synthesis in the BFR group 3 h post-exercise following four sets and 75 repetitions at 20% 1RM bilateral knee extensions, while no change was observed in the control group performing the identical protocol. More recently, Werbom et al. [106] reported a significant increase in mTOR signalling 1 hr post exercise following unilateral knee extension at 30% of 1RM to failure in the BFR trained leg compared to the control leg. While an enhanced
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mTOR signalling was observed following BFR training, it was also noted that there was no difference in mTOR signalling at 24 h post-exercise between both conditions. Therefore, it may be difficult to assess the influence of mTOR signalling in concert with systemic responses and local growth factors [107]. Resistance exercise and systemic hypoxia Hypoxic exercise is alternative training method where the amount of oxygen available to the muscle is reduced by breathing hypoxic air, has been reported to improve both aerobic [108] and anaerobic [109] performance in athletes. Additionally, it has also been shown that power output can be improved following high-intensity cycling in hypoxia [110], while others have found substantial improvements in muscular strength [111, 112]. Given that the aim of BFR is to reduce the oxygen delivery and availability to the muscle to create a localised hypoxic environment, it is possible that similar responses may be observed when performing resistance exercise in systemic hypoxia [111]. Physiological responses to resistance training in hypoxia Muscle cross sectional area While RTH is in its infancy, there a few studies that have reported augmented changes in muscle CSA [111-114]. A novel study that compared the effects of 5 wk of low-intensity (20% 1RM) resistance
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