ROLE OF PLACENTAL LATOGEN IN FETAL DEVELOPMENT

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Recent studies from this laboratory have demonstrated that the metabolic and somatotropic effects of placental lactogen (PL) in fetal tissues are mediated through binding of the hormone to a distinct and unique PL receptor. We now propose to investigate the regulation of the PL receptor in human fetal tissues in vitro and in ovine fetal liver in vivo. The roles of various hormones and growth factors in the regulation of the human PL receptor will be examined in studies of the binding of radiolabeled human PL (hPL) to human fetal myoblasts and hepatocytes. These studies will examine the effects of insulin, the insulin-like growth factors, hPL, thyroxine, hydrocortisone and the sex steroids on the number and affinity of hPL receptors in cultured cells. The role of nutritional factors in the regulation of PL receptors in vivo will be examined in studies of the binding of radiolabeled ovine PL to ovine fetal liver microsomes. These studies will examine the effects of maternal fasting and fetal hyperglycemia on the number and affinity of fetal oPL receptors. The effects of maternal fasting or fetal hyperglycemia on fetal oPL receptors will be related to changes in the plasma concentrations of glucose, insulin, insulin-like growth factors I and II, oPL, oGH and oPRL in the fetal lamb and to changes in fetal hepatic DNA and glycogen content. The hormonal and nutritional effects on PL receptors in human fetal tissues in vitro and in ovine fetal liver in vivo will be compared to effects on fetal epidermal growth factor recetors. These studies of the regulation of the fetal PL receptor in vitro and in vivo should provide insight into the factors which control PL action in the fetus. Since PL has growth-promoting effects in fetal tissues, these studies should contribute to our understanding of the hormonal control of fetal growth. Studies of the effects of maternal fasting on fetal PL receptors may clarify the mechanisms by which maternal fasting and malnutrition give rise to fetal growth retardation. Conversely, studies of the effects of fetal hyperglycemia (and concomitant fetal hyperinsulinemia) on fetal PL receptors may provide new insight into the pathogenesis of fetal macrosomia in pregnancies complicated by maternal diabetes mellitus.