The History of the Insulin-Like Growth Factor System

Horm Res Paediatr. 2022;95(6):619-630. doi: 10.1159/000527123. Epub 2022 Nov 29.


The growth hormone (GH)-insulin-like growth factor (IGF) cascade is central to the regulation of growth and metabolism. This article focuses on the history of the components of the IGF system, with an emphasis on the peptide hormones, IGF-I and -II, their cell surface receptors, and the IGF binding proteins (IGFBPs) and IGFBP proteases that regulate the availability of the peptide hormones for interaction with their receptors in relevant target tissues. We describe landmark events in the evolution of the somatomedin hypothesis, including evidence that has become available from experiments at the molecular and cellular levels, whole animal and tissue-specific gene knockouts, studies of cancer epidemiology, identification of prismatic human cases, and short- and long-term clinical trials of IGF-I therapy in humans. In addition, this new evidence has expanded our clinical definition of GH insensitivity (GHI) beyond growth hormone receptor mutations (classic Laron syndrome) to include conditions that cause primary IGF deficiency by impacting post-receptor signal transduction, IGF production, IGF availability to interact with the IGF-I receptor (IGF-1R), and defects in the IGF-1R, itself. We also discuss the clinical aspects of IGFs, from their description as insulin-like activity, to the use of IGF-I in the diagnosis and treatment of GH deficiency, and to the use of recombinant human IGF-I for therapy of children with GHI.

Keywords: Acid labile subunit; Growth hormone insensitivity; IGF binding protein; IGF deficiency; Insulin-like growth factor; Insulin-like growth factor receptor 1; Pregnancy associated plasma protein A/A2; hIGF-1 therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Insulin-Like Growth Factor I* / deficiency
  • Insulin-Like Growth Factor I* / history
  • Insulin-Like Growth Factor I* / physiology
  • Insulin-Like Growth Factor I* / therapeutic use
  • Insulin-Like Growth Factor II* / deficiency
  • Insulin-Like Growth Factor II* / history
  • Insulin-Like Growth Factor II* / physiology
  • Insulin-Like Growth Factor II* / therapeutic use
  • Laron Syndrome* / drug therapy
  • Laron Syndrome* / genetics
  • Laron Syndrome* / history
  • Laron Syndrome* / physiopathology
  • Peptide Hormones
  • Protein Processing, Post-Translational
  • Signal Transduction
  • Somatomedins / deficiency
  • Somatomedins / history
  • Somatomedins / physiology


  • Insulin-Like Growth Factor I
  • Peptide Hormones
  • Somatomedins
  • Insulin-Like Growth Factor II