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

TLDR

The somatomedin hypothesis posits that hepatic insulin‑like growth factor I (IGF‑I) is a key circulating mediator of growth hormone essential for postnatal growth and development. The authors sought to reassess this hypothesis by eliminating hepatic IGF‑I. They achieved liver‑specific igf1 deletion using Cre/loxP recombination. Loss of hepatic igf1 abolished hepatic IGF‑I expression and markedly reduced circulating IGF‑I, yet body weight, length, and femur length were unchanged, demonstrating that circulating IGF‑I is not required for normal postnatal growth and underscoring the role of autocrine/paracrine IGF‑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.