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Growth hormone resistance in uremia, a role for impaired JAK/STAT signaling

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Abstract

Resistance to growth hormone (GH) is a significant complication of advanced chronic renal failure. Thus while the circulating GH levels are normal or even elevated in uremia, resistance to the hormone leads to stunting of body growth in children and contributes to muscle wasting in adults. Insensitivity to GH is the consequence of multiple defects in the GH/insulin-like growth factor-1 (IGF-1) system. Expression of the GH receptor may be reduced, although this is not a consistent finding, GH activation of the Janus kinase 2-signal transducer (JAK2) and activator of transcription (STAT) signal transduction pathway is depressed and this leads to reduced IGF-1 expression, and finally there is resistance to IGF-1, a major mediator of GH action. We review these various defects with an emphasis on the GH-activated JAK2-STAT5 pathway, since this pathway is essential for normal body growth and there has been recent progress in our understanding of the perturbations that occur in uremia.

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Acknowledgements

This review and work from the authors′ laboratory were supported by a Merit Review Grant from the Research Service of the Department of Veterans Affairs and funding from the American Heart Association and a Norman S. Coplon Grant from Satellite Research. Apologies are extended in advance to those authors who are not referenced in this review because of its relative brevity.

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Authors and Affiliations

  1. Veterans Affairs, Palo Alto Health Care System, Palo Alto, California, USA

    Ralph Rabkin

  2. Department of Medicine, Stanford University, Stanford, California, USA

    Ralph Rabkin, Di Fei Sun, Yu Chen & Jane Tan

  3. Division of Pediatric Nephrology, University Children’s Hospital, Heidelberg, Germany

    Franz Schaefer

  4. Veterans Affairs, Palo Alto Health Care System 111R, Palo Alto, CA 94304, USA

    Ralph Rabkin

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  1. Ralph Rabkin
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  2. Di Fei Sun
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  3. Yu Chen
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  4. Jane Tan
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  5. Franz Schaefer
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Corresponding author

Correspondence to Ralph Rabkin.

Additional information

This work was presented in part at the IPNA Seventh Symposium on Growth and Development in Children with Chronic Kidney Disease: The Molecular Basis of Skeletal Growth, 1–3 April 2004, Heidelberg. Germany

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Rabkin, R., Sun, D.F., Chen, Y. et al. Growth hormone resistance in uremia, a role for impaired JAK/STAT signaling. Pediatr Nephrol 20, 313–318 (2005). https://doi.org/10.1007/s00467-004-1713-8

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  • DOI: https://doi.org/10.1007/s00467-004-1713-8

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