CHOLESTEROL UPTAKE VS SYNTHESIS BY GUINEA PIG ADRENAL

豚鼠肾上腺的胆固醇摄取与合成

• 批准号: 3152613
• 负责人: VIRGINIA H BLACK
• 金额: $ 10.58万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 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/3152613
• 关键词: acetyl coA; adrenal glands; autoradiography; bioassay; cell type; cholesterol; hormone regulation /control mechanism; radiotracer; steroid hormone biosynthesis; tissue /cell culture

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。 该前体可以从血浆脂蛋白或通过内源性获得 合成。 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 细胞的种类和动物的种类。 迄今为止，研究已 集中在整个肾上腺。 然而，不同的带状细胞类型 它们的摄取也可能有所不同：胆固醇的合成并受到调节 对于这个函数是有区别的。 有人认为，类固醇分泌细胞具有丰富的 脂滴从血浆中吸收大部分胆固醇（Fruhling 等人，1973），而那些拥有丰富的光滑表面内质 网织自身合成很大一部分胆固醇。 两者都不 这些假设已被直接检验。 豚鼠的肾上腺有 三种不同的带状细胞类型：具有丰富脂质的束状带 飞沫;网状带具有丰富的光滑网状结构；肾小球带 脂质很少，缺乏光滑网状结构。 于是豚鼠 肾上腺为差异摄取与合成提供了理想的测试系统 皮质细胞类型之间。 本提案的目的是使用 分离豚鼠肾上腺带状细胞类型以检查 从摄取获得的胆固醇与类固醇内源合成的胆固醇 生物合成。 肾上腺皮质细胞的过氧化物酶体，与肾上腺皮质细胞相关的小细胞器 光滑的网状结构，含有与脂肪酸β氧化系统分开的脂肪酸 线粒体中的线粒体，它响应促肾上腺皮质激素（ACTH）而增加活性。 豚鼠肾上腺提供了一个极好的组织来进行研究 该酶系统产生的乙酰辅酶A的利用程度 用于从头合成胆固醇。