IGF1 does not overcome sexual dimorphism of body and muscle size in Mstn−/− mice

in Journal of Endocrinology
Authors:
Ryan Paul University of Auckland Waikato Clinical School, Hamilton, New Zealand

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Kim Whiteman ManukaMed LP, Hamilton, New Zealand

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Shelley J Falconer AgResearch Ltd, Hamilton, New Zealand

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Jenny M Oldham AgResearch Ltd, Hamilton, New Zealand

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Ferenc Jeanplong AgResearch Ltd, Hamilton, New Zealand

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Kenneth G Matthews AgResearch Ltd, Hamilton, New Zealand

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Heather K Smith Department of Exercise Sciences, University of Auckland, Auckland Mail Centre, Auckland, New Zealand

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Mark Thomas ManukaMed LP, Hamilton, New Zealand

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Trevor Watson AgResearch Ltd, Hamilton, New Zealand

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Christopher D McMahon ManukaMed LP, Hamilton, New Zealand
AgResearch Ltd, Hamilton, New Zealand

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https://orcid.org/0000-0003-3635-177X

Correspondence should be addressed to C D McMahon: mcmahonc@xtra.co.nz
DOI:
https://doi.org/10.1530/JOE-20-0485
Volume/Issue:
Volume 248: Issue 2
Article Type:
Research Article
Page Range:
207–220
Online Publication Date:
Feb 2021
Copyright:
© 2021 Society for Endocrinology 2021
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Insulin-like growth factor-1 (IGF1) is crucial for regulating post-natal growth and, along with myostatin (MSTN), 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 (from 2 to 6 weeks) were unchanged, thereafter, to 32 weeks of age in WT 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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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2021 Society for Endocrinology 2021
Page(s):
14
Article Type:
Research Article
Received Date:
26 Nov 2020
Accepted Date:
08 Dec 2020
Print Publication Date:
01 Feb 2021
Online Publication Date:
Feb 2021
Keywords:
skeletal muscle; AKT; growth; myofibre hypertrophy; myofibre hyperplasia; GH; STAT5B; IGF1; IGF1 receptors; myostatin; sexual dimorphism

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