Regulatory gene expression in skeletal muscle of highly endurance-trained humans.

Abstract

Changes in regulatory and structural gene expression provide the molecular basis for the adaptation of human skeletal muscle to endurance exercise. The steady-state levels of multiple mRNAs mainly involved in regulatory functions differ between highly endurance-trained and untrained subjects in a muscle heavily recruited during the exercise. Biopsies from musculus vastus lateralis of seven untrained (UT) subjects [maximal oxygen consumption (VO2max) = 39 mL kg-1 min-1] and seven trained (T) professional cyclists (VO2max = 72 mL kg-1 min-1) were analysed for the contents of 597 different mRNAs using commercially available cDNA arrays (Clontech no. 7740-1). Intra-individual expression profiles were compared by least-square linear regression analysis. Differences in gene expression between the two groups were tested for statistical significance using L1 regression analysis combined with the sign test on all permutations of scatter plots of log raw values from UT vs. T subjects. Transcripts for 144 of 597 genes were sufficiently abundant to be analysed quantitatively. The expression profiles of the T group had a better intragroup correlation (R2) than those of the UT group (0.78 vs. 0.65, P < 0.05). An intergroup (T vs. UT) correlation of expression profiles gave an R2 of 0.71. Statistical analysis at a false discovery rate of 5% identified differential expression of nine cell-regulatory genes between T and UT. The mRNA levels of eight genes, including two DNA repair enzymes, transcription factors, signal transducers, a glycolytic enzyme and a factor involved in steroid hormone metabolism were increased in T vs. UT. Conversely, the mRNA of the tumour suppressor APC was downregulated with endurance training. Selective reverse-transcriptase polymerase chain reaction experiments confirmed the signal estimates from the array analysis. The repetitive impact of the complex exercise stimuli in professional cyclists attenuated the interindividual differences in regulatory gene expression in skeletal muscle. Long-term nuclear reprogramming of regulatory gene expression seems to be characteristic of human musculus vastus lateralis in a highly endurance-trained steady state.