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The decrease in mature myostatin protein in male skeletal muscle is developmentally regulated by growth hormone

Myostatin inhibits myogenesis and there is reduced abundance of the mature protein in skeletal muscles of adult male compared with female mice. This reduction probably occurs after translation, which suggests that it is a regulated mechanism to reduce the availability of myostatin in males. Reduced...

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Published in:The Journal of physiology 2009-02, Vol.587 (3), p.669-677
Main Authors: Oldham, Jenny M., Osepchook, Claire C., Jeanplong, Ferenc, Falconer, Shelley J., Matthews, Kenneth G., Conaglen, John V., Gerrard, David F., Smith, Heather K., Wilkins, Richard J., Bass, James J., McMahon, Christopher D.
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container_title The Journal of physiology
container_volume 587
creator Oldham, Jenny M.
Osepchook, Claire C.
Jeanplong, Ferenc
Falconer, Shelley J.
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Gerrard, David F.
Smith, Heather K.
Wilkins, Richard J.
Bass, James J.
McMahon, Christopher D.
description Myostatin inhibits myogenesis and there is reduced abundance of the mature protein in skeletal muscles of adult male compared with female mice. This reduction probably occurs after translation, which suggests that it is a regulated mechanism to reduce the availability of myostatin in males. Reduced myostatin may, thereby, contribute to the development of sexually dimorphic growth of skeletal muscle. Our first objective was to determine if the decrease in mature myostatin protein occurs before the linear growth phase to aid growth, or afterwards to maintain the mass of adult muscle. Mice were killed from 2 to 32 weeks and the gastrocnemius muscle was excised. Myostatin mRNA increased from 2 to 32 weeks and was higher in males than females ( P < 0.001). In contrast, mature protein decreased in males after 6 weeks ( P < 0.001). Our second objective was to determine if growth hormone (GH) induces the decrease in mature myostatin protein. GH increased myostatin mRNA and decreased the abundance of mature protein in hypophysectomised mice ( P < 0.05). Our final objective was to determine if the decrease in mature protein occurs in skeletal muscles of male Stat5b −/− mice (Stat5b mediates the actions of GH). As expected, mature myostatin protein was not reduced in Stat5b −/− males compared with females. However, myostatin mRNA remained higher in males than females irrespective of genotype. These data suggest that: (1) the decrease in mature myostatin protein is developmentally regulated, (2) GH acting via Stat5b regulates the abundance of mature myostatin and (3) GH acts via a non-Stat5b pathway to regulate myostatin mRNA.
doi_str_mv 10.1113/jphysiol.2008.161521
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subjects Animals
Body Weight
Down-Regulation
Female
Gene Expression Regulation, Developmental
Growth Hormone - metabolism
Male
Mice
Mice, Knockout
Muscle Development - physiology
Muscle, Skeletal - growth & development
Muscle, Skeletal - metabolism
Myostatin - genetics
Myostatin - metabolism
Sex Characteristics
Skeletal Muscle And Exercise
STAT5 Transcription Factor - deficiency
STAT5 Transcription Factor - genetics
title The decrease in mature myostatin protein in male skeletal muscle is developmentally regulated by growth hormone
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