Myostatin is a skeletal muscle target of growth hormone anabolic action.
Journal Title: Journal of Clinical Endocrinology and Metabolism - Year 2003, Vol 88, Issue 11
Abstract
Myostatin is a cytokine that has recently been shown to selectively andpotently inhibit myogenesis. To investigate the mechanisms of anabolic actions of GH on skeletal musclegrowth, we examined the in vitro and in vivo effects of GH on myostatin regulation. Twelve GH-deficienthypopituitary adult subjects were treated with recombinant GH (5 micro g/kg.d) in a double-blind, placebo-controlledfashion. Body composition and physical function were assessed and skeletal muscle biopsies from the vastuslateralis performed at 6-monthly intervals during 18 months of treatment. Myostatin mRNA expression wassignificantly 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-phosphatedehydrogenase gene. The inhibitory effect of GH on myostatin was sustained after 12 and 18 months ofGH treatment. These effects were associated with increases in lean body mass and translated into enhancedaerobic performance as determined by maximal oxygen uptake and ventilation threshold. Parallel in vitrostudies of skeletal muscle cells demonstrated significant reduction of myostatin expression by myotubesin response to GH, compared with vehicle treatment. Conversely, GH receptor antagonism resulted in up-regulationof myostatin in myoblasts. Given the potent catabolic actions of myostatin, our data suggest that myostatinrepresents a potential key target for GH-induced anabolism.
Authors and Affiliations
Wei Liu, Scott G Thomas, Sylvia L Asa, Nestor Gonzalez-Cadavid, Shalendar Bhasin, Shereen Ezzat
Keywords
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