Reduced pericellular sensitivity to IGF-I in fibroblasts from girls with Turner syndrome: a mechanism to impair clinical responses to GH

Pediatr Res. 2011 Jul;70(1):25-30. doi: 10.1203/PDR.0b013e31821b570b.

Abstract

Girls with Turner syndrome (TS) are treated with supraphysiological doses of growth hormone (GH) to improve final height; however in some girls, the growth response can be poor. This may reflect aberrations in GH and/or IGF-I actions at the cellular level, and thus this study compared the response of skin fibroblasts from normal children (n = 5) and girls with TS (n = 8) to GH, IGF-I, or a combination, by assessing the IGF binding protein (IGFBP) profile of conditioned medium harvested over 7 d. The two cell types had a comparable IGFBP profile; IGFBP-3 and IGFBP-4 were the most abundant species. TS fibroblasts produced more IGFBP-3 (d 7, 51.4 ± 45 ng/mL versus 20 ± 22 ng/mL; p < 0.05) than control cells; levels of IGFBP-4 were similar (21 ± 12 ng/mL versus 30 ± 21 ng/mL). GH did not influence IGFBP production. IGF-I treatment did not affect IGFBP-4 levels but enhanced the production of IGFBP-3 by both cell types (p < 0.05). However, the response of TS fibroblasts to IGF-I was approximately half that observed in normal cells (p < 0.05). Altered IGF-I activity, because of reduced bioavailability and/or reduced sensitivity, could contribute to the need for high GH doses in TS and for the poor response to GH in some girls with TS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Cells, Cultured
  • Female
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Growth Hormone / therapeutic use*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 2 / metabolism
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Protein 4 / metabolism
  • Insulin-Like Growth Factor Binding Protein 5 / metabolism
  • Insulin-Like Growth Factor Binding Proteins / metabolism
  • Insulin-Like Growth Factor I / metabolism*
  • Janus Kinase 2 / metabolism
  • Phosphorylation
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology
  • Time Factors
  • Turner Syndrome / drug therapy*
  • Turner Syndrome / metabolism
  • Turner Syndrome / pathology

Substances

  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 2
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Protein 4
  • Insulin-Like Growth Factor Binding Protein 5
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • JAK2 protein, human
  • Janus Kinase 2