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

Weiguo Yao, Kathleen Bethin, Xianlin Yang, Jin Zhong, Wei Hua Lee

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)227-234
Number of pages8
JournalEndocrine
Volume32
Issue number2
DOIs
StatePublished - Oct 1 2007

Keywords

  • GH administration
  • IGF-I
  • Stat5b
  • Weaver mice

ASJC Scopus subject areas

  • Endocrinology

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    Yao, W., Bethin, K., Yang, X., Zhong, J., & Lee, W. H. (2007). Role of the GH/IGF-I axis in the growth retardation of weaver mice. Endocrine, 32(2), 227-234. https://doi.org/10.1007/s12020-007-9003-4