Nutritional regulation of the placental lactogen receptor in fetal liver: implications for fetal metabolism and growth

Abstract

We have recently identified and purified from fetal liver a distinct receptor that mediates the effects of placental lactogen (PL) on amino acid transport, glycogen synthesis, and somatomedin production in fetal tissues. At present, the factors that regulate the number and affinity of PL receptors in the fetus are unknown. Since maternal nutrition plays a critical role in fetal metabolism and growth, we have examined the role of nutrition in the regulation of the PL receptor in fetal lambs. Pregnant ewes at 123-126 days gestation were fed ad libitum (FED), fasted for 3 days (FASTED), or fasted for 3 days and then refed for an additional 3 days (REFED). The ewes were then killed, and the binding of [125I]ovine (o) PL to hepatic microsomes from the fetal lambs was examined. Maternal fasting caused a 60-75% reduction in the specific binding of oPL to fetal liver; the effect of fasting was reversed in part by refeeding [specific binding per mg protein: FED, 11.8 +/- 2.2% (n = 8); FASTED, 2.8 +/- 0.4% (n = 7); REFED, 7.2 +/- 2.6% (n = 3)]. The decrease in oPL binding resulted from an 80% reduction in the number of fetal oPL-binding sites (Scatchard analysis); there were no changes in the affinity of the oPL receptor (Kd, 0.6 nM), the subunit structure of the receptor, or the degree of occupancy of the receptor in vivo by endogenous fetal hormones. The specific bindings of GH (0.6%), PRL (0.3%), and insulin (35%) to fetal liver were not affected by maternal fasting, indicating that caloric restriction exerted a specific effect on oPL binding in the fetus. The number of fetal oPL-binding sites was positively correlated with the fetal liver glycogen content (r = 0.69; P less than 0.01) and the fetal plasma concentrations of glucose (r = 0.68; P less than 0.01) and insulin-like growth factor-I (r = 0.74; P less than 0.001), suggesting a role for the PL receptor in the regulation of fetal carbohydrate metabolism and growth. The number of fetal PL receptors was inversely correlated with the fetal plasma oPL concentration (r = 0.47; P less than 0.05). These studies demonstrate that fasting of the pregnant ewe reduces the number of PL receptors in ovine fetal liver. The reduction in fetal hepatic PL receptors may contribute to the mobilization and depletion of fetal liver glycogen stores and may play a role in the pathogenesis of the fetal growth retardation that accompanies maternal caloric deprivation.