PRIMATE ENDOCRINE REGULATION IN THE PERINATAL PERIOD

灵长类动物围产期内分泌调节

基本信息

批准号：
6329862
负责人：
ROBERT B JAFFE
金额：
$ 28.64万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-06-01 至 2003-11-30
项目状态：
已结题

项目摘要

The goal of these studies is to elucidate the developmental biology of the human fetal adrenal gland. Our underlying hypothesis is that the unique structure, rate of growth and steroidogenic function of the human fetal adrenal is the net effect of ACTH secreted from the fetal pituitary and a cohort of growth factors expressed by the fetal adrenal of which insulin-like growth factor-II (IGF-II) is a major component. Based upon our preliminary findings and those of others, our specific aims are to determine: the mechanisms by which the fetal adrenals grows; the functions of the various cortical zones; the mechanism by which ACTH regulates growth and function; and the role of IGF-II in fetal growth and function. Understanding the growth and differentiation of the fetal adrenal gland is to cardinal importance because of 1) the pivotal role adrenal corticosteroids play in early enzyme induction, the coordinate development of independent organ systems necessary or intrauterine homeostasis and extrauterine survival (e.g. feta lung maturation, deposition of glycogen in the fetal liver, and induction of enzymes in the fetal brain, thyroid, gastrointestinal tract and retina), the response to intrauterine and perinatal stress; 2) the pathologic alteration of growth that occurs in congenital adrenal hyperplasia, which we hypothesize is the result of the overexpresion of locally produced growth factors stimulated by excess ACTH; 3) the atavistic reversion to a fetal mode of function in adult adrenal neoplasms; and 4) the insights into more general aspects of human organ growth that this understanding will provide. We will utilize cell culture and molecular biological techniques, as well as two newly develop;ed in vivo models (fetal adrenal tissue grafted under the kidney capsule of the athymic mouse and endogenous stimulation of the hypothalamic-pituitary-adrenal axis of the fetal rhesus monkey) to address our specific aims concerning the developmental biology of the human fetal adrenal gland. The proposed studies are to investigate specific aspects of growth and differentiation in the human fetal adrenal with the aim of determining the mechanism by which these processes are regulated. Ultimately, these adrenal with the aim of determining the mechanisms by which these process are regulated. Ultimately, these studies should contribute to knowledge of the role of the fetal adrenal in intrauterine development and homeostasis, the regulation of normal and altered human pregnancy, as well as greater understanding of the mechanisms of trophic hormone action on target tissue.

这些研究的目的是阐明人类胎儿肾上腺。我们的基本假设是人类的独特结构，生长速率和类固醇生成功能胎儿肾上腺是胎儿垂体分泌的ACTH的净效应以及由胎儿肾上腺表达的一系列生长因子胰岛素样生长因子-II（IGF-II）是主要组成部分。根据我们的初步发现和其他发现，我们的具体发现目的是确定：胎儿肾上腺增长的机制；各个皮质区的功能； ACTH的机制调节生长和功能； IGF-II在胎儿生长和功能。了解胎儿肾上腺的生长和分化由于1）关键作用肾上腺是基本的重要性皮质类固醇在早期酶诱导中发挥作用，坐标开发独立器官系统必需或宫内体内平衡和外部生存（例如，羊乳肺成熟，糖原在胎儿肝脏中的沉积和酶的诱导胎儿大脑，甲状腺，胃肠道和视网膜），对宫内和围产期应激的反应； 2）病理学先天性肾上腺增生发生的生长改变，这我们假设是本地生产过度主张的结果过量ACTH刺激的生长因子； 3）Atavistic归还到成人肾上腺肿瘤的胎儿功能模式； 4）见解进入人体器官增长的更一般方面，这种理解将提供。我们还将利用细胞培养和分子生物学技术随着两个新发展的体内模型（胎儿肾上腺组织移植在无胸腺小鼠和内源性刺激的肾脏胶囊下胎儿鼠尾草的下丘脑 - 垂体 - 肾上腺轴）解决我们有关有关发展生物学的特定目标人胎儿肾上腺。拟议的研究旨在研究增长的特定方面人类胎儿肾上腺的分化，目的是确定这些过程受到调节的机制。最终，这些肾上腺旨在确定这些过程的机制受调节。最终，这些研究应该有助于知识胎儿肾上腺在宫内发育中的作用稳态，对正常和人类怀孕改变的调节，以及对营养激素作用机制的更多了解在目标组织上。