THE ROLE OF PLACENTAL LACTOGEN IN FETAL DEVELOPMENT

胎盘催乳素(PL)具有直接代谢和促生长作用 胎儿组织，这表明该激素在控制 胎儿发育。磷脂酶在胎儿中的生物学作用是由 至少部分是通过荷尔蒙与一种不同的PL结合 受体。这项建议的总体目标是研究 在细胞水平上对PL受体的调节。初步研究将 绵羊胚胎中磷脂酶及其受体的结合和加工 肝细胞，绵羊和人胎儿成纤维细胞。具体实验 将决定内化、降解和再循环的速度 放射性配体及其受体。随后的研究将检查 不同激素与生长对胎儿组织磷脂结合的调节 胰岛素、胰岛素样生长因子、磷脂酶原、甲状腺 荷尔蒙、糖皮质激素和性激素。特异性抗血清 胰岛素和IGF-I受体将被用来确定 胰岛素对PL结合的影响是通过胰岛素受体介导的 或IGF-I受体。IGF-II的效果将与那些 胰岛素和IGF-I的作用，以阐明IGF-II及其 受体在调节磷脂结合中的作用。胎盘早孕对胎儿IGF-I的影响 将在胎儿肝细胞和胎儿体内检测IGF-II的产生 和特定的实验将确定是否影响成纤维细胞 胰岛素和其他激素增强PL对胎儿IGF产生的影响 这增加了PL结合。这些研究应该提供新的信息 关于磷脂酰胆碱受体的生理和调节，并可能澄清 磷脂酰胆碱在调节胎儿生长发育中的作用自PL以来 在胎儿组织中发挥代谢和促进生长的作用，这些 研究可能为胎儿新陈代谢的调节提供新的见解 胎儿生长的控制。

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.