THE ROLE OF PLACENTAL LACTOGEN IN FETAL DEVELOPMENT

胎盘泌乳素在胎儿发育中的作用

• 批准号: 3324660
• 负责人: MICHAEL S. FREEMARK
• 金额: $ 8.82万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-05-01 至 1991-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3324660
• 关键词: diet; embryo /fetus; embryo /fetus tissue /cell culture; epidermal growth factor; fasting; gel electrophoresis; gestational diabetes mellitus; growth factor; hormone binding protein; hormone receptor; hormone regulation /control mechanism; human fetus tissue; human tissue; hyperglycemia; mammalian embryology; nutrition related tag; placental hormones; pregnancy disorder; prenatal growth disorder; radioimmunoassay; radionuclides; scintillation spectrometry; sheep; somatomammotropin; statistics /biometry

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.

该实验室最近的研究表明， 胎盘催乳素（PL）的代谢和促生长作用， 胎儿组织是通过激素与一种 独特的PL受体。 我们现在提议调查 PL受体在体外人胎儿组织中的调节作用 和绵羊胎肝的体内试验。 各种激素的作用， 生长因子在调节人PL受体中的作用 在放射性标记的人PL（hPL）结合研究中检查 人胎儿成肌细胞和肝细胞。 这些研究将 研究胰岛素，胰岛素样生长因子， hPL、甲状腺素、氢化可的松和性类固醇的数量 和hPL受体在培养细胞中的亲和力。 的作用 营养因子在体内PL受体的调节将是 在放射性标记绵羊PL与 羊胎肝微粒体。 这些研究将审查 母亲禁食和胎儿高血糖对胎儿生长发育的影响 胎儿oPL受体的数量和亲和力。 的影响 母体空腹或胎儿高血糖对胎儿oPL受体的影响 将与血浆葡萄糖浓度的变化有关， 胰岛素、胰岛素样生长因子I和II、oPL、oGH和oPRL， 胎儿肝脏DNA和糖原的变化 内容 激素和营养对PL受体的影响 体外人胎儿组织和体内羊胎肝将 与对胎儿表皮生长因子受体的影响相比。 这些研究的调控胎儿PL受体在体外 在体内的实验应该能让我们深入了解 PL在胎儿中的作用。 由于PL具有促生长作用， 胎儿组织，这些研究应该有助于我们理解 荷尔蒙对胎儿生长的控制 影响的研究 母体禁食对胎儿PL受体的影响可能阐明 产妇禁食和营养不良导致 胎儿发育迟缓 相反，研究 胎儿高血糖症（伴胎儿高胰岛素血症） 胎儿PL受体可能提供新的见解的发病机制， 妊娠合并母体 糖尿病的