ONTOGENESIS OF CONTROL OF SOMATOMEDIN SECRETION

本项目旨在阐明正常的调节机制。 胎儿发育。10%的人类怀孕会导致发育迟缓 婴儿发病率、死亡率和先天畸形增加。 通常情况下，原因无法确定，也不存在共识 荷尔蒙可能起着关键作用。一种独特的胎儿生长抑素(SM)是 有可能。我们的主要目标是继续检验这一假设 胎儿SM是由生长激素以外的激素控制的。而当 我们已经发现了两种可能的候选激素，糖皮质激素和表皮生长 我们决定将研究重点放在后者上。其他 表明胎儿形式的EGF在发育和发育过程中 肿瘤过程。我们是第一个建议它作为SM的监管者的人 分泌物。我们的具体目标是：1)调节SM的激素 随胎龄变化？2)SM载体蛋白在 胎儿生长发育？3)SM与EGF在调节中的关系 胎儿发育？大鼠肝细胞将从不同胎龄的胎儿中分离出来 胎龄，并在不同激素的培养中孵化， 尤其是EGF和地塞米松。条件性细胞有丝分裂活性的研究 培养基用~3H-胸腺嘧啶核苷掺入DNA进行检测。 总SM水平将通过竞争性蛋白结合试验进行监测 不区分不同的SM。为了描述 胎儿SM分泌，其水平将由更特异的大鼠评估 胰岛素样生长因子-II(MSA)和胰岛素样生长因子-I(SM-C)放射免疫分析。两国之间的关系 SM的分泌和激素与胎儿肝细胞的结合将 学习。SM载体蛋白似乎也调节SM的作用。我们会 研究它们的激素调节和生化特性， 它们的血清水平与胎儿大小的关系及其影响 丹参的促有丝分裂活性。最后，EGF与SM的关系 在调节胎儿生长发育方面将进行评估。将测量EGF水平 用生物测定法、放射受体测定法和放射免疫测定法测定胎儿血清和 与SM水平及胎儿大小相关。胎儿EGF将从 胎鼠及其对SM分泌的影响与成年EGF的比较。 所了解的信息应提供科学依据，以便 可以设计出减少胎儿生长迟缓的临床方法。

This project is designed to elucidate the mechanisms regulating normal fetal growth. Ten percent of human pregnancies result in growth-retarded infants, who have increased morbidity, mortality and congenital anomalies. Usually, the cause cannot be identified and no consensus exists as to which hormones might play critical roles. A unique fetal somatomedin (SM) is one possibility. Our primary objective is to continue to test the hypothesis that fetal SM is controlled by hormones other than growth hormone. While we have found two likely candidates, glucocorticoids and epidermal growth factor (EGF), we have decided to focus our studies on the latter. Others have implicated a fetal form of EGF in both the developmental and neoplastic processes. We are the first to suggest it as a regulator of SM secretion. Our specific aims are: 1) Do the hormones which regulate SM change with gestational age? 2) What is the role of SM carrier proteins in fetal growth? 3) What is the relationship between SM and EGF in regulating fetal growth? Rat hepatocytes will be isolated from fetuses of different gestational ages and incubated in culture with various hormones, particularly EGF and dexamethasone. Mitogenic activity of conditioned medium will be assayed by the incorporation of 3H-thymidine into DNA. Total SM levels will be monitored by a competitive protein binding assay which does not discriminate between the various SM's. To characterize the fetal SM secretion, its levels will be assessed by the more specific rat IGF-II (MSA) and IGF-I (SM-C) radioimmunoassays. The relationship between SM secretion and hormonal binding to fetal hepatocytes will then be studied. SM carrier proteins also appear to modulate SM action. We will study their hormonal regulation and biochemical properties, the relationship between their levels in serum and fetal size, and their effect on mitogenic activity of SM. Lastly, the relationship between EGF and SM in regulating fetal growth will be evaluated. EGF levels will be measured by bioassay, radioreceptor assay, and radioimmunoassay in fetal serum and correlated with SM levels and fetal size. Fetal EGF will be extracted from fetal rats and its effect on SM secretion compared to that of adult EGF. The information learned should provide a scientific basis from which clinical methods can be devised to decrease fetal growth retardation.