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.
KeywordsWeaver mice IGF-I GH administration Stat5b
This study was supported by NIH, R01 NS40314, Riley Children Foundation, and Lilly Endowment. We also thank the support from Minor in Aging Fellowship from School of Medicine at IUPUI and the Grants-in-Aid of Research (GIAR) grant from Sigma-Xi.
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