ROLE OF PLACENTAL LACTOGEN IN FETAL DEVELOPMENT

胎盘泌乳素在胎儿发育中的作用

• 批准号: 2194384
• 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/2194384
• 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)具有直接代谢和营养生长作用。 胎儿组织，这表明该激素在控制 胎儿发育。磷脂酰胆碱在胎儿中的生物学作用是药物作用的 通过与一种独特的磷脂酶受体结合。整体而言 这项建议的目的是检查生理和调节 在细胞和分子水平上的PL受体。该基因的信使核糖核酸 绵羊PL受体将使用从绵羊磷脂酰胆碱受体中分离的cDNA探针进行鉴定 羊胎肝基因文库。母血清白蛋白受体基因表达水平的研究 胎儿绵羊组织将在怀孕的不同阶段进行检查 确定在开发过程中PL的绑定是否发生变化 通过改变PL受体mRNA的表达。监管 将研究营养和激素因素对PL受体mRNA的影响 绵羊胎肝和母羊肝体内及绵羊胎肝细胞内 体外培养。这些研究应该会产生关于生理学的新信息。 在分子水平上研究PL受体，并可能有助于阐明 不同激素和营养物质调节基因表达的机制 妊娠母羊和胎羔羊的PL受体的表达。因为PL有 在胎儿组织中的促生长作用，这些研究也应该 提供对正常和正常胎儿生长控制机制的洞察 病理性怀孕。为了对分子进行研究 关于PL受体的生物学，我已经征求了专家的帮助 在分子内分泌学方面有丰富经验。此外，作为一个主要的 作为RCDA的组成部分，我计划休15个月的假，以便在 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 加强我作为胎儿疾病领域独立调查员的职业生涯 内分泌学。