Submitted on June 26, 2007
Accepted on November 21, 2007
Effect of gender on human MEF2 regulation during endurance exercise
Kristian Vissing1*, Sean L McGee2, Carsten Roepstorff3, Peter Schjerling4, Mark Hargreaves2, and Bente Kiens3
1 Dept. of Sport Science, University of Aarhus, Copenhagen, Denmark
2 Dept. of Physiology, University of Melbourne, Parville, Victoria, Australia
3 Dept. of Human Physiology, Copenhagen Muscle Research Centre, University of Copenhagen, Copenhagen, Denmark
4 Dept. of Molecular Muscle Biology, Copenhagen Muscle Research Centre, Rigshospitalet, Copenhagen, Denmark; Dept. of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
* To whom correspondence should be addressed. E-mail: vissing{at}idraet.au.dk.
Women exhibit an enhanced capability for lipid metabolism during endurance exercise compared to men. The underlying regulatory mechanisms behind this gender difference are not understood, but may comprise signaling through a myocyte enhancer factor 2 (MEF2) regulatory pathway. The primary purpose of this study was therefore to investigate the protein signaling of MEF2 regulatory pathway components at rest and during 90 min bicycling exercise at 60% VO2peak in healthy, moderately trained men (n=8) and women (n=9) to elucidate the potential role of these proteins in substrate utilization during exercise. A secondary purpose was to screen for mRNA expression of MEF2-isoforms and myogenic regulatory factor (MRF) family members of transcription factors at rest and during exercise Muscle biopsies were obtained before and immediately after exercise. Nuclear 
AMPK Thr172 (p<0.001), HDAC5 Ser498 (p<0.001) and Thr pMEF2 (p<0.01) phosphorylation increased with exercise. No significant gender differences were observed at rest or during exercise. At rest, no significant gender differences were observed in mRNA expression of the measured transcription factors. mRNA for transcription factors MyoD, myogenin, MRF4, MEF2A, MEF2C, MEF2D and PGC1 were significantly upregulated by exercise. Of these, MEF2A mRNA increased 25% specifically in women (p<0.05), while MEF2D mRNA tended to increase in men (p=0.11). While minor gender differences in mRNA expression were observed, the main finding of the present study was the implication of a joint signaling action of AMPK, HDAC5 and PGC1 on MEF2 in the immediate regulatory response to endurance type exercise. This signaling response was independent of gender.
