THE ROLE OF PLACENTAL LACTOGEN IN FETAL DEVELOPMENT

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Placental lactogen (PL) has direct metabolic and somatotropic effects in fetal tissues, suggesting that the hormone plays a role in the control of fetal growth. The biological actions of PL in the fetus are mediated, at least in part, through the binding of the hormone to a distinct PL receptor. The overall objective of this proposal is to examine the regulation f the PL receptor at the cellular level. Initial studies will examine the binding and processing of PL and its receptor in ovine fetal hepatocytes and in ovine and human fetal fibroblasts. Specific experiments will determine the rates of internalization, degradation and recycling of the radioligand and its receptor. Subsequent studies will examine the regulation of PL binding in fetal tissues by various hormones and growth factors including insulin, the insulin-like growth factors, PL, thyroid hormone, the glucocorticoids and the sex steroids. Specific antisera to the insulin and IGF-I receptors will be employed to determine whether the effects of insulin on PL binding are mediated through the insulin receptor or the IGF-I receptor. The effects of IGF-II will be compared with those of insulin and IGF-I in order to clarify the role of IGF-II and its receptor in the regulation of PL binding. The effects of PL on fetal IGF-I and IGF-II production will be examined in fetal hepatocytes and fetal fibroblasts, and specific experiments will determine whether the effects of PL on fetal IGF production are potentiated by insulin and other hormones that increase PL binding. These studies should provide new information about the physiology and regulation of the PL receptor and may clarify the role of PL in the regulation of fetal somatomedin production. Since PL exerts metabolic and growth-promoting effects in fetal tissues, these studies may provide new insight into the regulation of fetal metabolism and the control of fetal growth.