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Myostatin Gene Expression Is Reduced in Humans with Heavy-Resistance Strength Training: A Brief
Communication
Stephen M. Roth, Gregory F. Martel, Robert E. Ferrell, E. Jeffrey Metter, Ben F. Hurley and Marc A. Rogers
Exp Biol Med (Maywood) 2003 228: 706
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What is This?
This study examined changes in myostatin gene expression in mice and cattle (1–4). How myostatin influences muscle
response to strength training (ST). Fifteen young and older men phenotypes is unclear. Higher levels of myostatin immuno-
(n = 7) and women (n = 8) completed a 9-week heavy-resistance reactivity have been reported in the muscle and serum of
unilateral knee extension ST program. Muscle biopsies were
obtained from the dominant vastus lateralis before and after ST.
HIV-infected men with muscle wasting (5) and in the
In addition to myostatin mRNA levels, muscle volume and plasma of young men exposed to prolonged best rest (6).
strength were measured. Total RNA was reverse transcribed Reardon et al. (7) reported higher levels of myostatin
into cDNA, and myostatin mRNA was quantified using quanti- mRNA in muscle samples from patients with chronic disuse
tative PCR by standard fluorescent chemistries and was nor- atrophy associated with hip osteoarthritis compared with
malized to 18S rRNA levels. A 37% decrease in myostatin ex-
pression was observed in response to ST in all subjects com-
healthy control subjects. In rats, two reports have demon-
bined (2.70 ± 0.36 vs 1.69 ± 0.18 U, arbitrary units; P < 0.05). strated that myostatin expression is reduced from elevated
Though the decline in myostatin expression was similar regard- levels in response to reloading after atrophy-inducing con-
less of age or gender, the small number of subjects in these ditions (8, 9). Thus, increases in myostatin expression have
subgroups suggests that this observation needs to be con- been observed in conditions associated with muscle atro-
firmed. No significant correlations were observed between
myostatin expression and any muscle strength or volume mea-
phy, and myostatin expression appears to be responsive to
sure. Although further work is necessary to clarify the findings, muscle loading after atrophy.
these data demonstrate that myostatin mRNA levels are re- In the present study, we sought to determine whether
duced in response to heavy-resistance ST in humans. Exp Biol myostatin expression was altered by increased muscle load-
Med 228:706–709, 2003
ing in healthy individuals. Presumably, for muscle hyper-
Key words: GDF8; skeletal muscle; transcription trophy to occur in response to a stimulus, intrinsic regulators
of muscle cell size must be altered in some way. To address
this issue, we studied the response of myostatin expression
in humans to heavy-resistance strength training (ST), which
M
yostatin (growth and differentiation factor 8
[GDF8]) is a transforming growth factor- super- is associated with increases in muscle strength and mass
family member with importance as a negative (10, 11), and we hypothesized that ST would reduce myo-
growth regulator for skeletal muscle, such that mutations in statin expression.
the myostatin gene result in a hypermuscular phenotype in The subjects studied consisted of properly consented
young (20-30 years old; 4 men, 4 women) and older (65-75
years old; 3 men, 4 women) healthy, sedentary men and
This work was supported by the Competitive Medical Research Fund of the UPMC
Health System, Grants DK-46204 and AG-42148. S.R. was supported by Grant AG- women. All subjects performed a 9-week unilateral heavy-
05893. resistance ST program as previously described in detail
1
To whom requests for reprints should be addressed at Department of Kinesiology,
University of Maryland, College Park, MD 20742. E-mail: sroth1@umd.edu (12). Briefly, the training protocol consisted of unilateral ST
of the dominant leg performed by the knee extensors using
Received July 1, 2002. a Keiser K-300 pneumatic resistance machine 3 days per
Accepted January 7, 2003.
week. Each supervised ST session resulted in 50 completed
repetitions performed at near maximal resistance, thus re-
1535-3702/03/2286-0706$15.00
Copyright © 2003 by the Society for Experimental Biology and Medicine sulting in a highly strenuous muscle loading stimulus.
Specified rest periods (90-180 sec) were allowed between
sion in response to ST (P < 0.05), with no significant age or that myostatin mRNA levels would be reduced in response
gender differences. Figure 1 shows the individual responses to a program of heavy-resistance ST designed to increase
for each subject, demonstrating that the majority of indi- muscle mass and strength (i.e., inhibition of the growth
viduals showed a reduction in myostatin expression, with no inhibitor). Wehling et al. (8) demonstrated that periodic
gender differences in the response. Subjects with lower reloading of otherwise unloaded rat plantaris muscle re-
baseline levels of myostatin were more likely to show little sulted in less elevated myostatin levels (55% increase ver-
or no change in expression in response to ST. No significant sus ambulatory controls) compared with a continuously un-
relationships were observed between myostatin expression loaded condition (110% increase versus ambulatory con-
and muscle volume, strength, or body mass for either base- trols). Moreover, Lalani et al. (9) reported increased
line expression or change in expression in response to ST. myostatin mRNA and protein in several rat muscles in re-
The present study is the first to examine the influence sponse to microgravity, and a normalization of those levels
of muscle loading on myostatin expression in normally am- after the return to normal gravitation. Recent work by
bulatory, healthy human muscle. We observed a significant Kawada et al. (20) demonstrated that myostatin expression
decrease in myostatin expression in response to 9 weeks of was significantly reduced upon reloading of hindlimb sus-
heavy-resistance ST in previously sedentary, healthy men pended muscle in mice, with no change in expression in
and women. The ST-mediated decline in myostatin expres- response to either aging-related or unloading-induced atro-
sion appeared to be independent of age or gender, but the phy. These data indicate that myostatin is responsive to
small number of subjects in these subgroups will require muscle loading in some contexts, and thus might represent
additional studies to confirm that finding. an important cell size regulator for skeletal muscle.
Myostatin is well established as a negative regulator of In the present study, the issue was whether myostatin
muscle growth in animal models (16). The mechanism by expression was responsive to additional muscle loading in
which myostatin inhibits muscle growth is uncertain, al- normal, ambulatory (although sedentary) individuals. As
though Carlson et al. (17) and others (18, 19) have sug- Lalani et al. (9) postulate, a homeostatic balance likely ex-
gested an inhibitory effect on skeletal muscle satellite cells. ists between positive (e.g., insulin-like growth factors) and
We pursued the present investigation with the hypothesis negative (e.g., myostatin) growth regulators in skeletal