Bone homeostasis in growth hormone receptor-null mice is restored by IGF-I but independent of Stat5

J Clin Invest. 2000 Nov;106(9):1095-103. doi: 10.1172/JCI10753.


Growth hormone (GH) regulates both bone growth and remodeling, but it is unclear whether these actions are mediated directly by the GH receptor (GHR) and/or IGF-I signaling. The actions of GH are transduced by the Jak/Stat signaling pathway via Stat5, which is thought to regulate IGF-I expression. To determine the respective roles of GHR and IGF-I in bone growth and remodeling, we examined bones of wild-type, GHR knockout (GHR(-/-)), Stat5ab(-/-), and GHR(-/-) mice treated with IGF-I. Reduced bone growth in GHR(-/-) mice, due to a premature reduction in chondrocyte proliferation and cortical bone growth, was detected after 2 weeks of age. Additionally, although trabecular bone volume was unchanged, bone turnover was significantly reduced in GHR(-/-) mice, indicating GH involvement in the high bone-turnover level during growth. IGF-I treatment almost completely rescued all effects of the GHR(-/-) on both bone growth and remodeling, supporting a direct effect of IGF-I on both osteoblasts and chondrocytes. Whereas bone length was reduced in Stat5ab(-/-) mice, there was no reduction in trabecular bone remodeling or growth-plate width as observed in GHR(-/-) mice, indicating that the effects of GH in bone may not involve Stat5 activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Development / drug effects
  • Bone Development / genetics
  • Bone Development / physiology*
  • Bone Remodeling / drug effects
  • Bone Remodeling / genetics
  • Bone Remodeling / physiology*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Growth Hormone / deficiency*
  • Growth Hormone / genetics
  • Growth Hormone / physiology
  • Homeostasis
  • Humans
  • Insulin-Like Growth Factor I / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Milk Proteins*
  • Recombinant Proteins / pharmacology
  • STAT5 Transcription Factor
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Trans-Activators / physiology


  • DNA-Binding Proteins
  • Milk Proteins
  • Recombinant Proteins
  • STAT5 Transcription Factor
  • Trans-Activators
  • Insulin-Like Growth Factor I
  • Growth Hormone