Normal Growth and Development in the Absence of Hepatic Insulin-like Growth Factor I

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1999 Jun 23

PMID 10377413

Citations 410

Authors

S Yakar

J L Liu

B STANNARD

A Butler

D Accili

B Sauer

D LeRoith

Affiliations

Soon will be listed here.

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.

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