ONTOGENY OF HEPATIC TYPE-I INSULIN-LIKE GROWTH-FACTOR RECEPTORS IN THE RAT

We studied the pre- and postnatal developmental regulation of the hepatic type I IGF receptor in the rat. Fetal rat liver membranes bound IGF-I throughout the latter part of gestation (d 17 to 21). After birth, binding diminished rapidly, reaching barely detectable levels by the 13th postnatal d. However, the presence of type I IGF receptors was readily demonstrated by affinity-labeling throughout the immediate postnatal period and in adult rats. Furthermore, IGF-I-dependent autophosphorylation of type I receptors could be seen in both fetal and adult liver membranes. Fasting for 48 h in adult rats led to a 2-to 3-fold increase in affinity-labeled type I IGF receptors. In contrast, nutrient deprivation to the fetus, via maternal fasting, did not alter fetal hepatic IGF-I binding or affinity-labeling of the type I receptor. These results support a role for the IGF and the type I IGF receptor in the autocrine/paracrine regulation of hepatic growth through the latter stages of gestation in the rat. The demonstration of enzymatically active type I IGF receptors in adult liver, and their increased expression in fasted adult rats is consistent with an autocrine/paracrine role for hepatic IGF-I in the adult.