Endocrine Abstracts

We previously showed acute hypoxic conditions result in atrophy of myotubes in vitro. Chronic hypoxic exposure in vivo induces muscular atrophy in healthy mountaineering individuals and patients with COPD. Myotubes in vitro increase myostatin expression in response to hypoxic exposure. Further, hypoxic COPD patients show cachexia and increased serum myostatin expression. However, in vivo results are cofounded by disease factors in COPD patients or environmental factors in mountaineers. We therefore hypothesize that healthy normal individuals exposed to hypoxia will increase expression of serum and intramuscular myostatin protein. We exposed eight healthy males to 2 h of hypoxia (12% O₂) or control condition (21.93% O₂) in a cross-over design, separated by 14 days. Muscle biopsies and arterialised blood samples were taken pre-hypoxia (t=0), immediately post-hypoxia (t=120), and 3.3 h post-hypoxia (t=320). Plasma was analysed for total myostatin using a commercial ELISA. Bioactive myostatin peptide levels from biopsies was visualised by western blot in a standard manner.

Hypoxia successfully perturbed homeostasis, with saturation of capillary O₂ decreased across all time-points, increased heart rate during hypoxia, and trends towards increased LLAMS scores under hypoxic conditions. Analysed biopsies suggest a decrease in intramuscular myostatin at t=320 coupled with an increase in plasma myostatin concentration at t=320 as measured by plasma ELISA.

Hypoxic exposure is associated with myotube atrophy in vitro and muscle atrophy in vivo. Myostatin is an anti-anabolic protein that may underlie atrophy under hypoxic conditions. We suggest hypoxia stimulates muscle release of myostatin into the circulation where it has systemic effects. Further, if myostatin signalling is altered in healthy individuals during acute hypoxic exposure, this may explain the muscle atrophy seen in mountaineering and in diseases such as COPD.