IGF1 does not overcome sexual dimorphism of body and muscle size in Mstn-/- 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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:248 |
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| Enthalten in: |
The Journal of endocrinology - 248(2021), 2 vom: 09. Feb., Seite 207-220 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Paul, Ryan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.07.2021 Date Revised 20.07.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1530/JOE-20-0485 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM318613697 |
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| 100 | 1 | |a Paul, Ryan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a IGF1 does not overcome sexual dimorphism of body and muscle size in Mstn-/- mice |
| 264 | 1 | |c 2021 | |
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| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 20.07.2021 | ||
| 500 | |a Date Revised 20.07.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a AKT | |
| 650 | 4 | |a GH | |
| 650 | 4 | |a IGF1 | |
| 650 | 4 | |a IGF1 receptors | |
| 650 | 4 | |a STAT5B | |
| 650 | 4 | |a growth | |
| 650 | 4 | |a myofibre hyperplasia | |
| 650 | 4 | |a myofibre hypertrophy | |
| 650 | 4 | |a myostatin | |
| 650 | 4 | |a sexual dimorphism | |
| 650 | 4 | |a skeletal muscle | |
| 650 | 7 | |a Igf1r protein, mouse |2 NLM | |
| 650 | 7 | |a Myostatin |2 NLM | |
| 650 | 7 | |a insulin-like growth factor-1, mouse |2 NLM | |
| 650 | 7 | |a Insulin-Like Growth Factor I |2 NLM | |
| 650 | 7 | |a 67763-96-6 |2 NLM | |
| 650 | 7 | |a Receptor, IGF Type 1 |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-akt |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Whiteman, Kim |e verfasserin |4 aut | |
| 700 | 1 | |a Falconer, Shelley J |e verfasserin |4 aut | |
| 700 | 1 | |a Oldham, Jenny M |e verfasserin |4 aut | |
| 700 | 1 | |a Jeanplong, Ferenc |e verfasserin |4 aut | |
| 700 | 1 | |a Matthews, Kenneth G |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Heather K |e verfasserin |4 aut | |
| 700 | 1 | |a Thomas, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Watson, Trevor |e verfasserin |4 aut | |
| 700 | 1 | |a McMahon, Christopher D |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.1530/JOE-20-0485 |3 Volltext |
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