THE HORMONAL CONTROL OF FETAL GROWTH

激素和生长因子刺激体细胞的机制 人们对胎儿的发育情况知之甚少。大多数经典荷尔蒙 刺激出生后生长的物质似乎对 胎儿。在这个建议中，它是基于这样一个假设： 生长因子是胎儿生长发育的重要调节因子，强调 关于确定生长抑素在这一过程中的作用。我们有 丰富的胎儿和产后生长激素研究经验 依赖有丝分裂原，生长抑素-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，并将 胰岛素样生长因子的平行研究II.动物模型 对于宫内和新生儿生长迟缓，我们将尝试定义 黄曲霉体细胞生长与血清和组织浓度的关系 生长抑素和生长激素的结合。因为有越来越多的人 生长抑素通过自分泌和/或旁分泌起作用的证据 机制，我们建议测定体内生长抑素的浓度。 人类胎儿和新生儿，并将这些测量与血清联系起来 集中度和生长量。我们将进行旨在 定义胎儿体内生长原子素的细胞内形式，我们 将继续工作，以确定化学性质，生理 生长抑素结合蛋白的调节和生物学作用。vbl.使用 生长抑素的cdna探针，我们将开展细胞内的研究。 Sm-C/IGF-I基因表达的原位c DNA/m RNA定位 杂交，同时进行生长抑素的免疫细胞化学研究。 然后我们将继续量化生长激素在mRNAs中的浓度。 胎鼠和人的组织。我们希望通过这种方式来确定选址 以及胎儿体细胞的个体发育合成。此外，我们计划 生长抑素基因多态性与致病因素的关系 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基因探针。这些将是 旨在确定泛素mRNA在发育过程中的变化和 确定调节泛素基因表达的因子 发展。泛素在蛋白质降解中的独特作用及其可能 在转录中的作用使得它在胎儿生长过程中很可能是重要的 和发展。

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.