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1 Intramural Research Program, National Institute on Aging, National Institutes of Health; 2 Division of Endocrinology and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224; and 3 Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555
Growth hormone (GH),
insulin-like growth factor I (IGF-I), and testosterone (T) are
important mediators of muscle protein synthesis, and thus muscle mass,
all of which decline with age. We hypothesized that circulating
hormones would be related to the transcriptional levels of their
respective receptors and that this expression would be negatively
related to expression of the myostatin gene. We therefore determined
content of mRNA transcripts (by RT-PCR) for GH receptor (GHR), IGF-I,
androgen receptor (AR), and myostatin in skeletal muscle biopsy samples
from 27 healthy men >65 yr of age. There were no significant
relationships between age, lean body mass, or percent body fat and
transcript levels of GHR, IGF-I, AR, or myostatin. Moreover, there were
no significant correlations of serum GH, IGF-I, or T with their
corresponding target mRNA levels (GHR, intramuscular IGF-I, or AR) in
skeletal muscle. However, GHR was negatively correlated
(r =
0.60, P = 0.001) with myostatin
mRNA levels. The lack of apparent relationships of muscle transcripts
with their respective ligands in healthy older adults suggests that
age-related deficits in both GH and T may lead to an increase in
myostatin expression and a disassociation in autocrine IGF-I effects on
muscle protein synthesis, both of which could contribute to age-related sarcopenia.
androgens; reverse transcription-polymerase chain reaction; gene expression; elderly; protein metabolism
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