Comparison of GH, IGF-I, and testosterone with mRNA of receptors and myostatin in skeletal muscle in older men.
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.
Marcell
T J
TJ
Intramural Research Program, National Institute on Aging, National Institutes of Health, Maryland, USA. marcell@kronosinstitute.org
Harman
S M
SM
Urban
R J
RJ
Metz
D D
DD
Rodgers
B D
BD
Blackman
M R
MR
D000368:Aged; D000369:Aged, 80 and over; D001823:Body Composition / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D055435:Myostatin; D012333:RNA, Messenger / Q000096:biosynthesis*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D011944:Receptors, Androgen / Q000096:biosynthesis; D011986:Receptors, Somatotropin / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000097:blood / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
C525911:MSTN protein, human; D055435:Myostatin; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011986:Receptors, Somatotropin; D016212:Transforming Growth Factor beta; D019382:Human Growth Hormone; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D006854:Hydrocortisone