ONTOGENESIS OF CONTROL OF SOMATOMEDIN SECRETION

本项目旨在阐明调节正常 胎儿生长 10%的人类怀孕会导致发育迟缓 婴儿的发病率、死亡率和先天性畸形增加。 通常，无法确定原因，也无法就原因达成共识。 激素可能起着关键作用。 一种独特的胎儿生长调节素（SM）是一种 可能性 我们的主要目标是继续验证假设 胎儿SM是由生长激素以外的激素控制的。 而 我们发现了两个可能的候选者，糖皮质激素和表皮生长 EGF是一种天然的表皮生长因子，因此我们将重点放在后者上。 别人 EGF的胚胎形式在发育和 肿瘤过程 我们是第一个建议将其作为SM的监管者 分泌物 我们的具体目标是：1）调节SM的激素 随着胎龄的变化？ 2)SM载体蛋白在 胎儿发育 3)SM和EGF之间的关系是什么？ 胎儿发育 将从不同胎仔中分离大鼠肝细胞。 孕龄并在培养物中与各种激素一起孵育， EGF和地塞米松。 有丝分裂活性 将通过将3 H-胸苷掺入DNA来测定培养基。 将通过竞争性蛋白结合试验监测总SM水平 其不区分各种SM。 表征 胎儿SM分泌，其水平将通过更具体的大鼠进行评估 IGF-II（MSA）和IGF-I（SM-C）放射免疫测定。 的关系 SM分泌和激素与胎肝细胞的结合， 研究了 SM载体蛋白也似乎调节SM的行动。 我们将 研究它们的激素调节和生化特性， 血清中这两种激素水平与胎儿大小的关系及其对胎儿生长发育的影响 SM的促有丝分裂活性。 EGF与SM的关系 对胎儿生长的调节作用 EGF的含量将被检测 通过生物测定法、放射受体测定法和放射免疫测定法测定胎儿血清， 与SM水平和胎儿大小相关。 EGF是从胎儿中提取的。 胚胎大鼠和其对SM分泌的影响与成人EGF相比。 所了解的信息应提供科学依据， 可以设计临床方法来减少胎儿生长迟缓。

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.