title: Normal growth and development in the absence of hepatic insulin-like growth factor I.
abstract: The somatomedin hypothesis proposed that insulin-like growth factor I (IGF-I) was a hepatically derived circulating mediator of growth hormone and is a crucial factor for postnatal growth and development. To reassess this hypothesis, we have used the Cre/loxP recombination system to delete the igf1 gene exclusively in the liver. igf1 gene deletion in the liver abrogated expression of igf1 mRNA and caused a dramatic reduction in circulating IGF-I levels. However, growth as determined by body weight, body length, and femoral length did not differ from wild-type littermates. Although our model proves that hepatic IGF-I is indeed the major contributor to circulating IGF-I levels in mice it challenges the concept that circulating IGF-I is crucial for normal postnatal growth. Rather, our model provides direct evidence for the importance of the autocrine/paracrine role of IGF-I.
authors.affiliation: Section on Cellular and Molecular Physiology, Molecular and Cellular Endocrinology Branch, National Institutes of Health, Bethesda, MD 20892-1770, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yakar
authors.forename: J L
authors.initials: JL
authors.lastname: Liu
authors.forename: B
authors.initials: B
authors.lastname: Stannard
authors.forename: A
authors.initials: A
authors.lastname: Butler
authors.forename: D
authors.initials: D
authors.lastname: Accili
authors.forename: B
authors.initials: B
authors.lastname: Sauer
authors.forename: D
authors.initials: D
authors.lastname: LeRoith
mesh_terms: D000818:Animals; D001835:Body Weight; D005314:Embryonic and Fetal Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D019426:Integrases / Q000502:physiology; D008099:Liver / Q000196:embryology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D014764:Viral Proteins
chemical_list: D014764:Viral Proteins; D007334:Insulin-Like Growth Factor I; C045073:Cre recombinase; D019426:Integrases