Normal growth and development in the absence of hepatic insulin-like growth factor I

S Yakar, JL Liu, B Stannard, A Butler… - Proceedings of the …, 1999 - National Acad Sciences
S Yakar, JL Liu, B Stannard, A Butler, D Accili, B Sauer, D LeRoith
Proceedings of the National Academy of Sciences, 1999National Acad Sciences
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 …
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.
National Acad Sciences