The placental lactogen receptor in maternal and fetal sheep liver: regulation by glucose and role in the pathogenesis of fasting during pregnancy.
To clarify the roles of glucose and insulin in the regulation of the PL receptor in fetal and maternal sheep liver, we administered iv glucose to pregnant ewes during a 72-h fast. The binding of ovine PL (oPL) to hepatic membranes from glucose-infused ewes and their fetuses was compared with the binding of oPL to tissues of fasted, saline-infused sheep and sheep fed normally ad libitum. Fasting of pregnant ewes caused a 58-70% reduction in the number of PL receptors in fetal and maternal liver. Intravenous administration of glucose during fasting increased the number of PL receptors in fetal liver by 137.4%. In contrast, glucose administration during fasting had no effect on the number of PL receptors in maternal liver. The number of PL binding sites in fetal liver correlated positively with fetal weight (r = 0.59) and length (r = 0.54) and with fetal plasma glucose (r = 0.69) and insulin (r = 0.55) concentrations. In contrast, PL binding was inversely related to fetal plasma oPL concentrations (r = -0.70). These findings suggested that glucose, insulin, and/or oPL may regulate PL binding in the ovine fetus. To determine whether glucose or insulin exert direct effects on the PL receptor in ovine fetal tissues, we examined the binding of radiolabeled oPL to ovine fetal hepatocytes and fibroblasts in culture. The specific binding of oPL to fetal hepatocytes was low and variable (1.0 +/- 0.5%) and it was not possible to assess reliably the effects of glucose or insulin supplementation. The specific binding of oPL to fetal fibroblasts (5.4 +/- 0.6%/mg) was unaffected by variations in media glucose concentrations (5.5-16.5 mM) or by pretreatment with insulin (10-1000 ng/ml). The results of these studies demonstrate that glucose and other nutritional factors regulate the expression of the PL receptor in fetal and maternal sheep liver. Alterations in PL binding play roles in the metabolic adaptation of the mother and fetus to nutritional deprivation and stress.
Freemark, M; Keen, A; Fowlkes, J; Mularoni, T; Comer, M; Grandis, A; Kodack, L
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