Molecular adaptations in human skeletal muscle to endurance training undersimulated hypoxic conditions

This study was performed to explore changes in gene expression as a consequ ence of exercise training at two levels of intensity under normoxic and nor mobaric hypoxic conditions (corresponding to an altitude of 3,850 m). Four groups of human subjects trained five times a week for a total of 6 wk on a bicycle ergometer. Muscle biopsies were taken, and performance tests were carried out before and after the training period. Similar increases in maxi mal O-2 uptake (8.3-13.1%) and maximal power output (11.4-20.8%) were found in all groups. RT-PCR revealed elevated mRNA concentrations of the alpha - subunit of hypoxia-inducible factor 1 (HIF-1) after both high- (+82.4%) and low (+78.4%)-intensity training under hypoxic conditions. The mRNA of HIF- 1 alpha (736), a splice variant of HIF-1 alpha newly detected in human skel etal muscle, was shown to be changed in a similar pattern as HIF-1 alpha. I ncreased mRNA contents of myoglobin (+72.2%) and vascular endothelial growt h factor (+52.4%) were evoked only after high- intensity training in hypoxi a. Augmented mRNA levels of oxidative enzymes, phosphofructokinase, and hea t shock protein 70 were found after high- intensity training under both hyp oxic and normoxic conditions. Our findings suggest that HIF-1 is specifical ly involved in the regulation of muscle adaptations after hypoxia training. Fine-tuning of the training response is recognized at the molecular level, and with less sensitivity also at the structural level, but not at global functional responses like maximal O-2 uptake or maximal power output.