The somatomedin hypothesis: 2001.
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.
Le Roith
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Clinical Endocrinology Branch, National Institutes of Health, Bethesda, Maryland 20892-1758, USA. derek@helix.nih.gov
Bondy
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C
Yakar
S
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Liu
J L
JL
Butler
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A
D000818:Animals; D017353:Gene Deletion; D013006:Growth Hormone / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D011986:Receptors, Somatotropin / Q000502:physiology; D013002:Somatomedins / Q000502:physiology*
D011986:Receptors, Somatotropin; D013002:Somatomedins; D013006:Growth Hormone