Epiphyseal growth plate growth hormone receptor signaling is decreased in chronic kidney disease-related growth retardation

Ariel Troib, Daniel Landau, Leonid Kachko, Ralph Rabkin, Yael Segev

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Linear growth retardation in children with chronic kidney disease (CKD) has been ascribed to insensitivity to growth hormone. This resistance state has been attributed to impaired growth hormone signaling through the JAK2/STAT5 pathway in liver and skeletal muscle leading to reduced insulin-like growth factor-I (IGF-I). Here we determine whether systemic and growth plate alterations in growth hormone signaling contribute to CKD-induced linear growth retardation using partially nephrectomized and pair-fed control 20-day-old rats. Serum growth hormone did not change in rats with CKD, yet serum IGF-I levels were decreased and growth retarded. The tibial growth plate hypertrophic zone was wider and vascularization at the primary ossification center was reduced in CKD. This was associated with a decrease in growth plate vascular endothelial growth factor (VEGF) mRNA and immunostainable VEGF and IGF-I levels. Growth plate growth hormone receptor and STAT5 protein levels were unchanged, while JAK2 was reduced. Despite comparable growth hormone and growth hormone receptor levels in CKD and control rats, relative STAT5 phosphorylation was significantly depressed in CKD. Of note, the mRNA of SOCS2, an inhibitor of growth hormone signaling, was increased. Thus, linear growth impairment in CKD can in part be explained by impaired long bone growth plate growth hormone receptor signaling through the JAK2/STAT5 pathway, an abnormality that may be caused by an increase in SOCS2 expression.

Original languageEnglish
Pages (from-to)940-949
Number of pages10
JournalKidney International
Issue number5
StatePublished - 1 Jan 2013


  • IGF-I
  • STAT5
  • chronic kidney disease
  • growth hormone
  • growth plate
  • receptor
  • somatotropin

ASJC Scopus subject areas

  • Nephrology


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