4.5 Article

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

期刊

JOURNAL OF ENDOCRINOLOGY
卷 248, 期 2, 页码 207-220

出版社

BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-20-0485

关键词

skeletal muscle; AKT; growth; myofibre hypertrophy; myofibre hyperplasia; GH; STAT5B; IGF1; IGF1 receptors; myostatin; sexual dimorphism

资金

  1. Foundation of Research, Science and Technology (New Enterprise Research Fund), New Zealand [C10X0703]

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The study found that IGF1 plays an important role in regulating muscle growth during the rapid growth phase, and when myostatin is absent and IGF1 is in excess, there is a significant increase in body and muscle mass. However, sexual dimorphism still exists, with a more pronounced IGF1-induced activation of AKT in male mice.
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 overexpressing 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 AKT(S473) 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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