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CHOLESTEROL UPTAKE VS SYNTHESIS BY GUINEA PIG ADRENAL

豚鼠肾上腺的胆固醇摄取与合成

基本信息

批准号：
3231149
负责人：
VIRGINIA H BLACK
金额：
$ 10.19万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-03-01 至 1987-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3231149
关键词：
acetyl coA adrenal glands autoradiography bioassay cell type cholesterol hormone regulation /control mechanism radiotracer steroid hormone biosynthesis tissue /cell culture

项目摘要

Adrenocortical cells require cholesterol for steroid hormone synthesis. This precursor can be obtained from plasma lipoproteins or by endogenous synthesis. The proportion of the cholesterol utilized from these sources may depend on the availability of plasma liporoteins, the functional state of the cells, and the species of animal. Thus far, studies have concentrated on the whole adrenal. However, the different zonal cell types may also vary in their uptake: synthesis of cholesterol and be regulated differentially for this function. It has been suggested that steroid-secreting cells possessing abundant lipid droplets take up most of their cholesterol from the plasma (Fruhling et al, 1973), while those possessing abundant smooth-surfaced endoplasmic reticulum synthesize a large proportion of their own cholesterol. Neither of these hypotheses has been tested directly. The guinea pig adrenal has three distinct zonal cell types: zona fasciculata with abundant lipid droplets; zona reticularis with abundant smooth reticulum; zona glomerulosa with little lipid and a paucity of smooth reticulum. Thus the guinea pig adrenal provides an ideal test system for differential uptake vs synthesis among cortical cell types. It is the purpose of this proposal to use separated guinea pig adrenal zonal cell types to examine the ratio of cholesterol obtained from uptake vs endogenous synthesis for steroid biosynthesis. Peroxisomes of adrenocortical cells, small organelles associated with the smooth reticulum, contain a fatty acid Beta-oxidation systems separate from that in the mitochondria, which increases in activity in response to ACTH. The guinea pig adrenal provides an excellent tissue in which to investigate the extent to which acetyl CoA generated by this enzyme system is utilized for de novo cholesterol synthesis.

肾上腺皮质细胞需要胆固醇来合成类固醇激素。这种前体可以从血浆脂蛋白或通过内源性综合。从这些来源利用的胆固醇的比例可能取决于血浆脂蛋白的可用性、功能状态细胞和动物的物种。到目前为止，研究已经集中在整个肾上腺。然而，不同的带状细胞类型它们的摄取也可能不同：胆固醇的合成和受调控此功能的不同之处。已有研究表明，类固醇分泌细胞具有丰富的脂滴从血浆中吸收了大部分胆固醇(Fruhling 等)，而那些具有丰富的光滑表面内质的网状结构会合成很大比例的自身胆固醇。都不是这些假设中的一部分已经被直接测试过。豚鼠肾上腺有三种不同的带状细胞类型：富含脂肪的束状带液滴；网状带，有丰富的光滑网状物；球状带脂肪很少，光滑的网状结构稀少。因此，这只豚鼠肾上腺为区分摄取和合成提供了一个理想的测试系统在皮质细胞类型中。这项提议的目的是使用分离豚鼠肾上腺带细胞类型，检测其比例摄取胆固醇与内源性合成类固醇的比较生物合成。肾上腺皮质细胞的过氧化物体，与光滑的网状结构，含有一种独立的脂肪酸β-氧化体系在线粒体中，对ACTH的反应活性增加。豚鼠肾上腺为研究提供了极好的组织。该酶系统产生的乙酰辅酶A被利用的程度用于从头合成胆固醇。