THE HORMONAL CONTROL OF FETAL GROWTH

激素和生长因子刺激体细胞生长的机制 对胎儿的生长了解甚少。 大多数经典的激素 刺激产后生长的药物似乎对 胎儿 在这项提案中，它是基于这样的假设，即肽 生长因子是胎儿生长的重要介质，重点是 确定生长调节素在这一过程中的作用。 我们有 在生长激素的胎儿和产后研究方面拥有丰富的经验 生长调节素C/胰岛素样生长因子I (Sm-C/IGF-I）。 我们建议继续进行这些研究， 胰岛素样生长因子II的平行研究。 使用动物模型 对于宫内和新生儿生长迟缓，我们将尝试定义 体细胞生长、血清和组织浓度之间的关系 生长调节素和生长激素结合。 因为有越来越多 生长调节素通过自分泌和/或旁分泌发挥作用的证据 机制，我们建议，以确定浓度的生长调节素， 人胎儿和新生儿，并将这些测量值与血清 浓度和增长。 我们将进行实验， 定义胎儿中生长调节素的细胞内形式，我们 将继续致力于定义化学性质，生理 生长调节素结合蛋白的调节和生物学作用。 使用 cDNA探针的生长调节素，我们将进行研究的细胞 Sm-C/IGF-I基因原位cDNA/mRNA定位 杂交，与生长调节素的免疫细胞化学研究平行。 然后，我们将继续定量生长调节素mRNA的浓度， 胎鼠和人体组织。 我们希望通过这种方式来确定 和胎儿生长激素合成的个体发生。 此外，我们计划 表征引起疾病的生长调节素基因多态性 胎儿宫内发育迟缓 最后，我们将继续研究使用 我们最近描述的泛素前体cDNA探针。 这些将是 旨在确定发育过程中泛素mRNA的变化， 定义因子调节泛素基因的表达， 发展 泛素在蛋白质降解中的独特作用， 在转录中的作用使其在胎儿生长过程中可能是重要的 发展先行者的要求

The mechanisms by which hormones and growth factors stimulate the somatic growth of the fetus are poorly understood. Most of the classical hormones that stimulate postnatal growth appear to have little influence on the fetus. In this proposal, which is based on the supposition that peptide growth factors are important mediators of fetal growth, emphasis is placed on determining the role of the somatomedins in this process. We have extensive experience with fetal and postnatal studies of the growth hormone dependent mitogen, somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I). We propose to continue these studies and to incorporate parallel research on insulin-like growth factor II. Using animal models for intrauterine and neonatal growth retardation we will attempt to define the relationships among somatic growth, serus and tissue concentrations of the somatomedins, and growth hormone binding. Because there is growing evidence that the somatomedins act through autocrine and/or paracrine mechanisms, we propose to determine concentrations of the somatomedins in human fetuses and neonates, and to relate these measurements to serum concentrations and growth. We will carry out experiments designed to define the intracellular forms of the somatomedins in the fetus, and we will continue work directed at defining the chemical nature, physiological regulation and biologic actions of somatomedin binding proteins. Using cDNA probes for the somatomedins, we will carry out studies of cellular localization of expression of the Sm-C/IGF-I gene by in situ cDNA/mRNA hybridization, in parallel with immunocytochemical studies of somatomedin. We will then proceed to quantify concentrations of somatomedin mRNAs in fetal rat and human tissues. In this way we hope to determine the sites and ontogeny of fetal somatomedin syntheses. In addition, we plan to characterize somatomedin gene polymorphism in disorders causing intrauterine growth retardation. Finally, we will continue studies using our recently described ubiquitin precursor cDNA probe. These will be directed at determining changes in ubiquitin mRNA through development and defining factors that regulate expression of ubiquitin genes during development. Ubiquitin's unique role in protein degradation and possible role in transcription make it likely to be important during fetal growth and development.