ROLE OF PLACENTAL LACTOGEN IN FETAL DEVELOPMENT

胎盘泌乳素在胎儿发育中的作用

• 批准号: 3073496
• 负责人: MICHAEL S. FREEMARK
• 金额: $ 6.6万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3073496
• 关键词: complementary DNA; densitometry; embryo /fetus; embryo /fetus cell /tissue; gel electrophoresis; gestational age; hormone binding protein; hormone receptor; hormone regulation /control mechanism; liver; liver cells; mammalian embryology; messenger RNA; molecular cloning; nucleic acid probes; placental hormones; pregnancy disorder; prenatal growth disorder; receptor expression; sheep; somatomammotropin; statistics /biometry; tissue /cell culture

Placental lactogen (PL) has direct metabolic and somatotrophic 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 medicated through binding to a distinct and unique PL receptor. The overall objective of this proposal is to examine the physiology and regulation of the PL receptor at the cellular and molecular levels. The mRNA for the sheep PL receptor will be characterized using a cDNA probe isolated from a fetal sheep liver cDNA library. The levels of PL receptor mRNA in maternal and fetal sheep tissues will be examined at various stages of pregnancy to determine whether changes in the binding of PL during development result from changes in the expression of the PL receptor mRNA. The regulation of the PL receptor mRNA by nutritional and hormonal factors will be studied in fetal and maternal sheep liver in vivo and in ovine fetal hepatocytes in vitro. These studies should yield new information regarding the physiology of the Pl receptor at the molecular level and may help to clarify the mechanisms by which various hormones and nutrients regulate the expression of the PL receptor in the pregnant ewe and fetal lamb. Because PL has growth-promoting actions in fetal tissues, these studies should also provide insight into the mechanisms controlling fetal growth in normal and pathological pregnancies. In order to conduct studies of the molecular biology of the PL receptor, I have solicited the assistance of experts with extensive experience in molecular endocrinology. In addition, as a major component of the RCDA, I plan a 15 month sabbatical to obtain training in the theory and techniques of molecular biology. An RCDA would provide the time and opportunity to explore this new area of research and would thereby enhance my career as an independent investigator in the field of fetal endocrinology.

胎盘催乳素（PL）具有直接的代谢和促生长作用， 胎儿组织，这表明激素在控制 胎儿生长 PL在胎儿中的生物学作用是有药物作用的 通过与独特的PL受体结合。 整体 这项建议的目的是研究的生理和调节， PL受体在细胞和分子水平。 基因的mRNA 绵羊PL受体将使用分离自 胎羊肝cDNA文库 孕母胎盘组织中PL受体mRNA水平 在怀孕的各个阶段检查胎羊组织， 确定开发过程中PL绑定的变化是否导致 来自PL受体mRNA表达的变化。 调控 PL受体mRNA的营养和激素因素将在 体内胎儿和母体绵羊肝脏以及绵羊胎儿肝细胞中 体外 这些研究应该会产生新的信息， Pl受体在分子水平上的作用，可能有助于阐明 各种激素和营养物质调节表达的机制 妊娠母羊和胎儿羔羊的PL受体。 因为PL有 促进胎儿组织生长的作用，这些研究还应 提供了控制胎儿生长的机制，在正常和 病理性妊娠 为了进行分子研究 PL受体的生物学，我已经寻求专家的帮助， 在分子内分泌学方面有丰富的经验。 此外，作为一个主要 RCDA的组成部分，我计划15个月的休假，以获得培训， 分子生物学的理论和技术。 RCDA将提供 有时间和机会探索这一新的研究领域，从而 加强我作为胎儿领域独立调查员的职业生涯 内分泌学