Igf-I and postnatal growth of weaver mutant mice.

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Blotting-Western, Cerebellar-Ataxia, Female, Insulin-Like-Growth-Factor-Binding-Protein-3, Insulin-Like-Growth-Factor-I, Liver, Mice-Neurologic-Mutants, RNA-Messenger, Reverse-Transcriptase-Polymerase-Chain-Reaction, Sex-Factors, Sexual-Maturation

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Endocrine 2005 Mar; 26(2):117-25


IGF-I is an anabolic growth factor essential for growth and development, both as a mediator of growth hormone (GH) action and as a local stimulator of cell proliferation and differentiation. Although the importance of IGF-I in postnatal growth has been studied for several decades, its functions in pathological states are not fully understood. The weaver (wv) mutant mouse is a commonly used model for studying hereditary cerebellar ataxia and provides us with an opportunity to study the function of IGF-I in postnatal growth during neurodegeneration. In prepubertal wv mice, we found a parallel decrease in body weight and serum IGF-I. This parallel relationship was maintained in females, but not in males, as wv mice entered puberty. Interestingly, we found an increase in the levels of circulating IGF-I and hepatic mRNA preceded the catch-up of body weight of pubertal male wv mice. The increase in IGF-I levels coincided with a surge of circulating androgen at the onset of male puberty, suggesting that androgen might trigger the increase in IGF-I production in the pubertal and adult male wv mice. Overall, our results support the concept that IGF-I plays an important role in postnatal growth during and after neurodegeneration of wv mice. In addition, IGF-I's regulation of systemic growth during and after puberty is likely modulated by androgen in male wv mice.

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