IGF-1 does not overcome sexual dimorphism of body and muscle size in Mstn-/- mice

in Journal of Endocrinology
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  • 1 R Paul, Endocrinology, The University of Auckland Waikato Clinical School, Hamilton, New Zealand
  • 2 K Whiteman, ManukaMed Research Lab, ManukaMed LP, Hamilton, New Zealand
  • 3 S Falconer, Animal Productivity, AgResearch Ltd, Hamilton, New Zealand
  • 4 J Oldham, Growth and Development, AgResearch Ltd, Hamilton, New Zealand
  • 5 F Jeanplong, Growth and Development, AgResearch Ltd Ruakura Research Centre, Hamilton, New Zealand
  • 6 K Matthews, Growth and Development, AgResearch Ltd Ruakura Research Centre, Hamilton, New Zealand
  • 7 H Smith, Exercise Sciences, The University of Auckland, Auckland, New Zealand
  • 8 M Thomas, ManukaMed Research Lab, ManukaMed LP, Hamilton, New Zealand
  • 9 T Watson, Growth and Development, AgResearch Ltd Ruakura Research Centre, Hamilton, New Zealand
  • 10 C McMahon, Growth and Development, AgResearch Ltd Ruakura Research Centre, Hamilton, New Zealand

Correspondence: Christopher McMahon, Email: mcmahonc@xtra.co.nz

Insulin-like growth factor-1 (IGF1) is crucial for regulating post-natal growth and, along with myostatin, regulates muscle size. Here, we sought to clarify the roles of these two genes in regulating sexually dimorphic growth of body and muscle mass. In the first study, we established that Igf1 mRNA was increased to a greater extent and Igf1 receptor mRNA increased earlier in male, than in female, gastrocnemius muscles during the rapid phase of growth (2 to 6 weeks), but were unchanged, thereafter, to 32 weeks of age in wild-type mice (P<0.001). In the second study, we sought to determine if supplemental IGF1 could overcome the sexual dimorphism of muscle and body mass, when myostatin is absent. We crossed myostatin null (Mstn-/-) mice with mice over-expressing Igf1 in skeletal muscle (Igf1+) to generate six genotypes; control (Mstn+/+), Mstn+/-, Mstn-/-, Mstn+/+:Igf1+, Mstn+/-:Igf1+ and Mstn-/-:Igf1+ (n=8 per genotype and sex). In both sexes, body mass at 12 weeks was increased by at least 1.6-fold and muscle mass by at least 3-fold in Mstn-/-:Igf1+ compared with Mstn+/+ mice (P<0.001). The abundance of Akt was increased in muscles of mice transgenic for Mstn, while phosphorylation of AktS473 was increased in both male and female mice transgenic for Igf1+. The ratio of phosphorylated to total Akt was 1.9-fold greater in male mice (P<0.001). Thus, despite increased growth of skeletal muscle and body size when myostatin was absent and IGF1 was in excess, sexual dimorphism persisted, an effect consistent with greater IGF1-induced activation of Akt in skeletal muscles of males.

 

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