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

Judith S Renes1, Jaap van Doorn2, Anita C S Hokken-Koelega3,4

  • 1Department of Paediatrics, Subdivision of Endocrinology, Erasmus University Medical Centre, Sophia Children's Hospital, Rotterdam, The Netherlands, j.renes@erasmusmc.nl.

Hormone Research in Paediatrics
|September 12, 2019
PubMed

Insights

Growth hormone (GH) and insulin-like growth factor (IGF) axis issues may explain why some babies born small for gestational age (SGA) don't catch up in growth. Reduced IGF-I activity in utero and after birth is implicated.

Area of Science:

  • Pediatric endocrinology
  • Growth disorders
  • Molecular genetics

Background:

  • 10% of infants born small for gestational age (SGA) exhibit insufficient catch-up growth.
  • The underlying mechanisms for this growth failure are not fully understood.
  • Disruptions in the growth hormone (GH)-insulin-like growth factor (IGF) axis are suspected contributors.

Purpose of the Study:

  • To review molecular and genetic mechanisms of the GH-IGF axis in short children born SGA.
  • To elucidate the role of IGF system anomalies in SGA growth failure.

Main Methods:

  • Review of existing literature on GH-IGF axis in SGA.
  • Analysis of molecular and (epi)genetic factors.
  • Examination of IGF-I, IGF-binding proteins (IGFBP), and related components.

Main Results:

  • Lowered IGF-I levels in cord blood and placenta of SGA neonates.
  • Increased placental expression of IGFBP-1 and IGFBP-2, inhibiting IGF-I bioactivity.
  • Sustained reduced IGF-I, IGFBP-3, and acid-labile subunit levels in short SGA children.
  • Evidence of increased IGFBP-3 proteolysis.

Conclusions:

  • Suggests decreased in utero IGF-I bioactivity in SGA neonates.
  • Highlights persistent IGF-I axis dysregulation in SGA children with short stature.
  • Points to specific molecular anomalies within the IGF system as key factors in SGA growth failure.
Abstract

Keywords:
Acid-labile subunitGrowth hormoneInsulin-like growth factor binding proteinsSmall for gestational ageTernary complex formation

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