Role of the GH/IGF-I axis in the growth retardation of weaver mice.

Abstract

IGF-I is a well-established anabolic growth factor essential for growth and development. Although the role of the GH/IGF-I axis is established for normal postnatal growth, its functional state in neurodegenerative diseases is not fully characterized. The weaver mutant mouse is a commonly used model for studying hereditary cerebellar ataxia and provides an opportunity to investigate the function of IGF-I in postnatal growth following neurodegeneration. Previously, we reported that weaver mice are growth retarded and their body weights correlate with a decrease in circulating IGF-I levels. Because weaver mice have the same food intake/body weight ratios as their wild type littermates, our observation suggests that an impairment of the GH/IGF-I axis, rather than poor nutrition, likely contributes to their growth retardation. This study further investigated the etiology of reduced circulating IGF-I levels. We found that GH levels in weaver mice were reduced following acute insulin injection, but the hepatic GH receptor transduction pathway signaled normally as evidenced by increased STAT5b phosphorylation and IGF-I mRNA levels in response to acute GH administration. In addition, 2-week GH treatment induced a significant increase in body weight and circulating IGF-I levels in homozygous weaver mice but not in wild type littermates. In summary, a deficiency in the GH/IGF-I axis may be partially responsible for postnatal growth retardation in weaver mutant mice. This deficiency may occur at the level of the pituitary and/or hypothalamus and can be improved with GH administration.

• Authors: Weiguo Yao, Kathleen Bethin, Xianlin Yang, Jin Zhong, Wei-Hua Lee
• Journal: Endocrine (Endocrine) Vol. 32 Issue 2 Pg. 227-34 (Oct 2007) ISSN: 1355-008X [Print] United States
• PMID: 18040896 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• G Protein-Coupled Inwardly-Rectifying Potassium Channels
• Insulin
• Kcnj6 protein, mouse
• STAT5 Transcription Factor
• Stat5b protein, mouse
• Insulin-Like Growth Factor I
• Growth Hormone

Topics

• Animals
• Body Weight (drug effects)
• Disease Models, Animal
• Eating (drug effects)
• Female
• G Protein-Coupled Inwardly-Rectifying Potassium Channels (genetics)
• Gene Expression Regulation (drug effects)
• Growth Disorders (genetics, metabolism)
• Growth Hormone (metabolism, pharmacology)
• Insulin (pharmacology)
• Insulin-Like Growth Factor I (genetics, metabolism)
• Male
• Mice
• Mice, Neurologic Mutants
• Mutation
• Neurodegenerative Diseases (genetics, metabolism)
• Phosphorylation (drug effects)
• STAT5 Transcription Factor (metabolism)