Thesis
Myostatin regulation of the insulin-like growth factor axis
Washington State University
Master of Science (MS), Washington State University
2009
Handle:
https://hdl.handle.net/2376/100166
Abstract
Myostatin is a dynamic inhibitor of skeletal muscle growth in mammals, whose actions are largely attributed to autocrine effects. Recent studies have suggested that myostatin, which is produced in cardiac and skeletal muscle, has additional endocrine interactions due to its presence in circulation. While limited myostatin inhibition of the IGF axis in muscle has been characterized, systemic involvement with the IGF/IGFBP axis is unknown. We measured muscle, heart and liver transcript levels using qRT-PCR in neonate and adult wild type and mstn -/- animals. Neonatal skeletal muscle IGF1R and IGFBP-3 mRNA levels were elevated in mstn -/- animals. In adult gastrocnemius IGF1R and IGFBP-5 were elevated while those of IGF-I decreased while pectoralis IGFBP-3 levels were reduced. IGF1R and IGF-II mRNA levels were elevated in neonatal mstn -/- hearts, while adult hearts had a decrease in IGF1R. Myostatin regulation of the IGF axis in striated muscle is fiber type specific and reflects the state of tissue development. Increased IGF1R in all neonatal tissues may reflect enhanced IGF responsiveness and clarify why some mstn -/- muscles grow better than others. Levels of IGFR, IGFBP-3 and IGFBP-5 mRNA were all elevated in neonatal mstn-/- livers and IGF-I and IGFBP-3 levels were elevated in adults. Circulating levels of IGF-I were elevated in adults while IGFBP-2 were reduced. Myostatin affects endocrine production of liver IGF axis constituents, these constituents being responsible for mediating organismal growth and development. Additionally, the ratio of IGF binding proteins to IGF dropped, likely increasing IGF bioavailability and contributing to mstn knockout animal's double muscled phenotype. Additional experiments with recombinant glycosylated IGFBP-3 mutants characterized IGF -dependent and -independent effects on myoblast proliferation determined that IGF-dependent effects were largely responsible. These data together suggest that myostatin's influence on striated muscle growth includes local and systemic regulation of the IGF/IGFBP axis and that myostatin-induced changes in the muscle expression and circulating levels of IGFBPs likely influence muscle growth in an IGFdependent fashion.
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Details
- Title
- Myostatin regulation of the insulin-like growth factor axis
- Creators
- Nolann G. Williams
- Contributors
- Buel Dan Rodgers (Degree Supervisor)
- Awarding Institution
- Washington State University
- Academic Unit
- Molecular Biosciences, School of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University; Pullman, Wash. :
- Identifiers
- 99900525192601842
- Language
- English
- Resource Type
- Thesis