The somatomedin hypothesis: 2001

Endocr Rev. 2001 Feb;22(1):53-74. doi: 10.1210/edrv.22.1.0419.


Since the original somatomedin hypothesis was conceived, a number of important discoveries have allowed investigators to modify the concept. Originally somatic growth was thought to be controlled by pituitary GH and mediated by circulating insulin-like growth factor-I (IGF-I, somatomedin C) expressed exclusively by the liver. With the discovery that IGF-I is produced by most, if not all, tissues, the role of autocrine/paracrine IGF-I vs. the circulating form has been hotly debated. Recent experiments using transgenic and gene-deletion technologies have attempted to answer these questions. In the liverspecific igf-1 gene-deleted mouse model, postnatal growth and development are normal despite the marked reduction in circulating IGF-I and IGF-binding protein levels; free IGF-I levels are normal. Thus, the normal postnatal growth and development in these animals may be due to normal free IGF-I levels (from as yet unidentified sources), although the role of autocrine/paracrine IGF-I has yet to be determined.

Publication types

  • Review

MeSH terms

  • Animals
  • Gene Deletion
  • Growth Hormone / physiology
  • Humans
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Biological*
  • Receptors, Somatotropin / physiology
  • Somatomedins / physiology*


  • Receptors, Somatotropin
  • Somatomedins
  • Growth Hormone