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

The somatomedin hypothesis proposed that insulin-like growth factor I (IGF- I) uas a hepatically derived circulating mediator of growth hormone and is a crucial factor for postnatal growth and development. To reassess this hyp othesis, we hale used the Cre/loxP recombination system to delete the igf1 gene exclusively in the liver, igf1 gene deletion in the li, er abrogated e xpression of igf1 mRNA and caused a dramatic reduction in circulating IGF-I levels. However er, growth as determined by body weight, body length, and femoral length did not differ from wild-type littermates, Although our mode l 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 cr ucial for normal postnatal growth. Rather, our model provides direct eviden ce for the importance of the autocrine/paracrine role of IGF-I.