REGULATION OF LIPOPROTEIN METABOLISM BY SEX HORMONES

性激素对脂蛋白代谢的调节

• 批准号: 3348419
• 负责人: RAMPRATAP S KUSHWAHA
• 金额: $ 19.47万
• 依托单位: SOUTHWEST BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1988-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3348419
• 关键词: apolipoproteins; atherosclerosis; blood lipoprotein biosynthesis; blood lipoprotein metabolism; estrogens; female; high density lipoproteins; high performance liquid chromatography; immunoelectrophoresis; lipoprotein lipase; liver metabolism; low density lipoprotein; ovariectomy; progesterone; radionuclide double label; sex hormones; triacylglycerol lipase; triglycerides; very low density lipoprotein

Premenopausal women have a lower incidence of coronary heart disease than do males. This sex differential in atherosclerosis and coronary heart disease may, in part, be mediated by the effect of sex steroid hormones on lipoprotein levels in the plasma. The present studies are therefore proposed with the major objective to determine the mechanisms by which female sex steroid hormones regulate plasma lipoprotein metabolism and, in turn, influence atherosclerosis. Ovariectomized, adult baboons will be used to determine the effects of treatment with estrogen, progesterone, or a combination of estrogen and progesterone on the production and catabolism of lipoproteins and apoproteins. Simultaneous turnover studies of very low density (VLDL) and low density (LDL) lipoprotein apoprotein (apo) will be conducted by radiolabeling VLDL and LDL with different isotopes of iodine to determine the effect of hormonal treatment on the synthesis and catabolism of apo-B. To determine the effect of estrogens and progesterone on LDL removal pathways, turnover studies of modified LDL (cyclohexanedione treated LDL labeled with I131) and unmodified LDL (labeled with I125) will be conducted. Similarly, to determine the effect of treatment with female sex hormones on the synthesis and removal of apo-E and apo-A-I, turnover studies will conducted after iodinating isolated apoproteins and incorporating them into lipoproteins (VLDL and HDL). The kinetic data will be analyzed by modeling. The effect of sex steroid hormones will also be studied on postheparin plasma lipoprotein lipase and hepatic triglyceride lipase activities and triglyceride secretion. We will further determine if changes in lipoprotein metabolic parameters are mediated by hepatic estrogen receptors by measuring hepatic estrogen receptors in treated and untreated animals. Finally, the effect of lipoprotein pattern altered by estrogen, progesterone, or a combination, on the development of atherogenesis will be studied. Animals will be maintained on hormonal treatment for 18 months, after which they will be necropsied and arterial lesions will be measured.

绝经前女性冠心病发病率低于女性 做男性。 动脉粥样硬化和冠心病的性别差异 疾病可能部分是由性类固醇激素的作用介导的 血浆中的脂蛋白水平。 因此，目前的研究 提出的主要目标是确定机制 女性性类固醇激素调节血浆脂蛋白代谢， 转，影响动脉粥样硬化。 成年狒狒将被切除卵巢 用于确定雌激素、孕激素或雌激素治疗的效果 雌激素和孕激素的组合对产生和分解代谢的影响 脂蛋白和脱辅基蛋白。 非常低的同时营业额研究 密度（VLDL）和低密度（LDL）脂蛋白脱辅基蛋白（apo）将 通过用不同的碘同位素对 VLDL 和 LDL 进行放射性标记 确定激素治疗对合成和 apo-B 的分解代谢。 确定雌激素和孕激素的作用 关于 LDL 清除途径、改良 LDL（环己二酮）的周转研究 经处理的 LDL（用 I131 标记）和未修饰的 LDL（用 I125 标记）将 进行。 同样，为了确定女性治疗的效果 性激素对 apo-E 和 apo-A-I 的合成和去除、周转的影响 研究将在对分离的脱辅基蛋白进行碘化后进行 将它们整合到脂蛋白（VLDL 和 HDL）中。 动力学数据将 通过建模进行分析。 性类固醇激素的作用也会 肝素后血浆脂蛋白脂肪酶和肝甘油三酯的研究 脂肪酶活性和甘油三酯分泌。 我们将进一步确定是否 脂蛋白代谢参数的变化是由肝脏介导的 通过测量治疗组和治疗组的肝脏雌激素受体来检测雌激素受体 未经治疗的动物。 最后，脂蛋白模式的影响被改变 雌激素、孕激素或其组合，对发育的影响 将研究动脉粥样硬化形成。 动物将维持荷尔蒙 治疗18个月，之后将进行尸检并进行动脉供血 将测量病变。