Liver-derived insulin-like growth factor I (IGF-I) is the principal sourceof IGF-I in blood but is not required for postnatal body growth in mice

The body growth of animals is regulated by growth hormone and IGF-I, The cl assical theory of this regulation is that most IGF-I in the blood originate s in the liver and that body growth is controlled by the concentration of I GF-I in the blood, We have abolished IGF-I production in the livers of mice by using the Cre/loxP recombination system. These mice demonstrated comple te inactivation of the IGF-I gene in the hepatocytes, Although the liver ac counts for less than 5% of body mass, the concentration of IGF-I in the ser um was reduced by 75%, This finding confirms that the liver is the principa l source of IGF-I in the blood. However, the reduction in serum IGF-I conce ntration had no discernible effect on postnatal body growth. We conclude th at postnatal body growth is preserved despite complete absence of IGF-I pro duction by the hepatocytes.