Role of the GH/IGF-I axis in the growth retardation of weaver mice.
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.
Yao
Weiguo
W
Department of Pediatrics, Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Bethin
Kathleen
K
Yang
Xianlin
X
Zhong
Jin
J
Lee
Wei-Hua
WH
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006130:Growth Disorders / Q000235:genetics* / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D050799:STAT5 Transcription Factor / Q000378:metabolism
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D007328:Insulin; C497069:Kcnj6 protein, mouse; D050799:STAT5 Transcription Factor; C494096:Stat5b protein, mouse; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone