Liver-derived insulin-like growth factor I (IGF-I) is the principal source of 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 classical theory of this regulation is that most IGF-I in the blood originates in the liver and that body growth is controlled by the concentration of IGF-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 complete inactivation of the IGF-I gene in the hepatocytes. Although the liver accounts for less than 5% of body mass, the concentration of IGF-I in the serum was reduced by 75%. This finding confirms that the liver is the principal source of IGF-I in the blood. However, the reduction in serum IGF-I concentration had no discernible effect on postnatal body growth. We conclude that postnatal body growth is preserved despite complete absence of IGF-I production by the hepatocytes.

动物的机体生长受生长激素（growth hormone）与胰岛素样生长因子-I（IGF-I）调控。该调控过程的经典理论认为，血液中绝大多数胰岛素样生长因子-I来源于肝脏，且机体生长由血液中该因子的浓度所决定。我们借助Cre/loxP重组系统，实现了小鼠肝脏内胰岛素样生长因子-I合成的完全阻断，经验证，该类小鼠的肝细胞中胰岛素样生长因子-I基因已被彻底灭活。尽管肝脏仅占小鼠体重的5%以下，但其血清中的胰岛素样生长因子-I浓度却下降了75%。该结果证实，肝脏是血液中胰岛素样生长因子-I的主要来源。然而，血清胰岛素样生长因子-I浓度的降低，对小鼠出生后的机体生长并未产生可观测到的显著影响。综上我们得出结论：即便肝细胞完全无法合成胰岛素样生长因子-I，小鼠出生后的机体生长仍可维持正常。