A growth stimulus is needed for IGF-1 to induce skeletal muscle hypertrophy in vivo. 2010

Thea Shavlakadze, and Jinfen Chai, and Kirsten Maley, and Greg Cozens, and Griffin Grounds, and Nadine Winn, and Nadia Rosenthal, and Miranda D Grounds
School of Anatomy and Human Biology, The University of Western Australia, Perth 6009, WA, Australia. tshavlakadze@anhb.uwa.edu.au

Here, we characterise new strains of normal and dystrophic (mdx) mice that overexpress Class 2 IGF-1 Ea in skeletal myofibres. We show that transgenic mice have increased muscle levels of IGF-1 (approximately 13-26 fold) and show striking muscle hypertrophy (approximately 24-56% increase in mass). Adult normal muscles were resistant to elevated IGF-1; they reached adult steady state and maintained the same mass from 3 to 12 months. By contrast, dystrophic muscles from mdx/IGF-1(C2:Ea) mice continued to increase in mass during adulthood. IGF-1 signalling was evident only in muscles that were growing as a result of normal postnatal development (23-day-old mice) or regenerating in response to endogenous necrosis (adult mdx mice). Increased phosphorylation of Akt at Ser473 was not evident in fasted normal adult transgenic muscles, but was 1.9-fold higher in fasted normal young transgenic muscles compared with age-matched wild-type controls and fourfold higher in fasted adult mdx/IGF-1(C2:Ea) compared with mdx muscles. Muscles of adult mdx/IGF-1(C2:Ea) mice showed higher p70(S6K)(Thr421/Ser424) phosphorylation and both young transgenic and adult mdx/IGF-1(C2:Ea) mice had higher phosphorylation of rpS6(Ser235/236). The level of mRNA encoding myogenin was increased in normal young (but not adult) transgenic muscles, indicating enhanced myogenic differentiation. These data demonstrate that elevated IGF-1 has a hypertrophic effect on skeletal muscle only in growth situations.

UI MeSH Term Description Entries
D006984 Hypertrophy General increase in bulk of a part or organ due to CELL ENLARGEMENT and accumulation of FLUIDS AND SECRETIONS, not due to tumor formation, nor to an increase in the number of cells (HYPERPLASIA). Hypertrophies
D007334 Insulin-Like Growth Factor I A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D009137 Muscular Dystrophy, Animal MUSCULAR DYSTROPHY that occurs in VERTEBRATE animals. Animal Muscular Dystrophies,Animal Muscular Dystrophy,Dystrophies, Animal Muscular,Dystrophy, Animal Muscular,Muscular Dystrophies, Animal
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated

Related Publications

Thea Shavlakadze, and Jinfen Chai, and Kirsten Maley, and Greg Cozens, and Griffin Grounds, and Nadine Winn, and Nadia Rosenthal, and Miranda D Grounds
June 2010, Journal of applied physiology (Bethesda, Md. : 1985),
Thea Shavlakadze, and Jinfen Chai, and Kirsten Maley, and Greg Cozens, and Griffin Grounds, and Nadine Winn, and Nadia Rosenthal, and Miranda D Grounds
January 2012, Endocrinology,
Thea Shavlakadze, and Jinfen Chai, and Kirsten Maley, and Greg Cozens, and Griffin Grounds, and Nadine Winn, and Nadia Rosenthal, and Miranda D Grounds
January 1975, Recent advances in studies on cardiac structure and metabolism,
Thea Shavlakadze, and Jinfen Chai, and Kirsten Maley, and Greg Cozens, and Griffin Grounds, and Nadine Winn, and Nadia Rosenthal, and Miranda D Grounds
April 2012, Journal of cellular physiology,
Thea Shavlakadze, and Jinfen Chai, and Kirsten Maley, and Greg Cozens, and Griffin Grounds, and Nadine Winn, and Nadia Rosenthal, and Miranda D Grounds
August 2020, Cells,
Thea Shavlakadze, and Jinfen Chai, and Kirsten Maley, and Greg Cozens, and Griffin Grounds, and Nadine Winn, and Nadia Rosenthal, and Miranda D Grounds
February 2001, Nature genetics,
Thea Shavlakadze, and Jinfen Chai, and Kirsten Maley, and Greg Cozens, and Griffin Grounds, and Nadine Winn, and Nadia Rosenthal, and Miranda D Grounds
December 2005, Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology,
Thea Shavlakadze, and Jinfen Chai, and Kirsten Maley, and Greg Cozens, and Griffin Grounds, and Nadine Winn, and Nadia Rosenthal, and Miranda D Grounds
November 2013, Medicine and science in sports and exercise,
Thea Shavlakadze, and Jinfen Chai, and Kirsten Maley, and Greg Cozens, and Griffin Grounds, and Nadine Winn, and Nadia Rosenthal, and Miranda D Grounds
September 2015, American journal of physiology. Endocrinology and metabolism,
Thea Shavlakadze, and Jinfen Chai, and Kirsten Maley, and Greg Cozens, and Griffin Grounds, and Nadine Winn, and Nadia Rosenthal, and Miranda D Grounds
July 1999, The Journal of biological chemistry,
Copied contents to your clipboard!