Myostatin is a skeletal muscle target of growth hormone anabolic action.
Myostatin is a cytokine that has recently been shown to selectively and potently inhibit myogenesis. To investigate the mechanisms of anabolic actions of GH on skeletal muscle growth, we examined the in vitro and in vivo effects of GH on myostatin regulation. Twelve GH-deficient hypopituitary adult subjects were treated with recombinant GH (5 micro g/kg.d) in a double-blind, placebo-controlled fashion. Body composition and physical function were assessed and skeletal muscle biopsies from the vastus lateralis performed at 6-monthly intervals during 18 months of treatment. Myostatin mRNA expression was significantly inhibited to 31 +/- 9% (P < 0.001) of control by GH but not by placebo administration (79 +/- 11%) as determined by quantitative real-time PCR normalized for the housekeeping glyceraldehyde-3-phosphate dehydrogenase gene. The inhibitory effect of GH on myostatin was sustained after 12 and 18 months of GH treatment. These effects were associated with increases in lean body mass and translated into enhanced aerobic performance as determined by maximal oxygen uptake and ventilation threshold. Parallel in vitro studies of skeletal muscle cells demonstrated significant reduction of myostatin expression by myotubes in response to GH, compared with vehicle treatment. Conversely, GH receptor antagonism resulted in up-regulation of myostatin in myoblasts. Given the potent catabolic actions of myostatin, our data suggest that myostatin represents a potential key target for GH-induced anabolism.
Liu
Wei
W
Department of Medicine, Mount Sinai Hospital and University of Toronto, Ontario, Canada.
Thomas
Scott G
SG
Asa
Sylvia L
SL
Gonzalez-Cadavid
Nestor
N
Bhasin
Shalendar
S
Ezzat
Shereen
S
D000328:Adult; D000818:Animals; D015992:Body Mass Index; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D055435:Myostatin; D010101:Oxygen Consumption / Q000187:drug effects; D005082:Physical Exertion / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D011986:Receptors, Somatotropin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D016212:Transforming Growth Factor beta; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I