Current Insights into the Role of the Growth Hormone-Insulin-Like Growth Factor System in Short Children Born Small for Gestational Age

Horm Res Paediatr. 2019;92(1):15-27. doi: 10.1159/000502739. Epub 2019 Sep 11.

Abstract

Background: The reason for the insufficient catch-up growth seen in 10% of children born small for gestational age (SGA) is poorly understood. Disturbances in the growth hormone (GH) - insulin-like growth factor (IGF) axis might underlie this failure to show sufficient catch-up growth.

Conclusion: This review summarizes insights gained in the molecular and (epi) genetic mechanisms of the GH-IGF axis in short children born SGA. The most notable anomalies of the IGF system are the lowered IGF-I levels in both cord blood and the placenta, and the increased expression of IGF-binding proteins (IGFBP)-1 and IGFBP-2, which inhibit IGF-I, in the placenta of SGA neonates. These observations suggest a decreased bioactivity of IGF-I in utero. IGF-I levels remain reduced in SGA children with short stature, as well as IGFBP-3 and acid-labile subunit levels. Proteolysis of IGFBP-3 appears to be increased.

Keywords: Acid-labile subunit; Growth hormone; Insulin-like growth factor binding proteins; Small for gestational age; Ternary complex formation.

Publication types

  • Review

MeSH terms

  • Child
  • Epigenesis, Genetic*
  • Female
  • Human Growth Hormone* / genetics
  • Human Growth Hormone* / metabolism
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age / metabolism*
  • Insulin-Like Growth Factor Binding Proteins* / genetics
  • Insulin-Like Growth Factor Binding Proteins* / metabolism
  • Insulin-Like Growth Factor I* / genetics
  • Insulin-Like Growth Factor I* / metabolism
  • Male
  • Proteolysis*

Substances

  • IGF1 protein, human
  • Insulin-Like Growth Factor Binding Proteins
  • Human Growth Hormone
  • Insulin-Like Growth Factor I