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J Appl Physiol 103: 1488-1495, 2007. First published August 2, 2007; doi:10.1152/japplphysiol.01194.2006
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Load-mediated downregulation of myostatin mRNA is not sufficient to promote myofiber hypertrophy in humans: a cluster analysis

Jeong-su Kim,1,2 John K. Petrella,1,2 James M. Cross,3 and Marcas M. Bamman1,2

Departments of 1Physiology and Biophysics and 3Surgery, The University of Alabama at Birmingham, and 2Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center, Birmingham, Alabama

Submitted 22 October 2006 ; accepted in final form 1 August 2007

Myostatin is a potent inhibitor of myogenesis; thus differential expression might be expected across individuals varying in responsiveness to myogenic stimuli. We hypothesized that myostatin would be differentially regulated across humans with markedly different hypertrophic responses to resistance training (RT; 16 wk). Targets were assessed in muscle biopsies at baseline (T1) and 24 h after the first (T2) and last (T3) loading bouts in previously untrained subjects statistically clustered based on mean myofiber hypertrophy as extreme (Xtr; n = 17, 2,475 µm2), modest (n = 32, 1,111 µm2), and nonresponders (n = 17, –16 µm2). We assessed protein levels of latent full-length myostatin protein complex and its propeptide; mRNA levels of myostatin, cyclin D1, p21cip1, p27kip1, and activin receptor IIB; and serum myostatin protein concentration. Total RNA concentration increased by T3 in nonresponders (37%) and modest responders (40%), while it increased acutely (T2) only in Xtr (26%), remaining elevated at T3 (40%). Myostatin mRNA decreased at T2 (–44%) and remained suppressed at T3 (–52%), but not differentially across clusters. Cyclin D1 mRNA increased robustly by T2 (38%) and T3 (74%). The increase at T2 was driven by Xtr (62%, P < 0.005), and Xtr had the largest elevation at T3 (82%, P < 0.001). No effects were found for other target transcripts. Myostatin protein complex increased 44% by T3 (P < 0.001), but not differentially by cluster. Myostatin protein complex propeptide and circulating myostatin were not influenced by RT or cluster. Overall, we found no compelling evidence that myostatin is differentially regulated in humans demonstrating robust RT-mediated myofiber hypertrophy vs. those more resistant to growth.

resistance training; muscle growth; cell cycle; muscle fiber



Address for reprint requests and other correspondence: M. M. Bamman, UAB Dept. of Physiology and Biophysics, Core Muscle Research Laboratory, GRECC/11G, Veterans Affairs Medical Center, 1530 3rd Ave. South, Birmingham, AL 35294-0001 (e-mail: mbamman{at}uab.edu)




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