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.

绝经前妇女的冠状动脉疾病发病率低于 做男性。 动脉粥样硬化和冠状动脉心脏中的这种性别差异 疾病可能部分地通过性类固醇激素对 血浆中的脂蛋白水平。 因此，本研究是 提出的主要目标是确定 女性性类固醇激素调节血浆脂蛋白代谢，并在 转弯，影响动脉粥样硬化。 卵巢切除，成年狒狒 用于确定雌激素，孕酮或 雌激素和孕酮在生产和分解代谢中的结合 脂蛋白和丙蛋白。 同时对非常低的营业额研究 密度（VLDL）和低密度（LDL）脂蛋白磷蛋白（APO）将是 通过辐射标记VLDL和LDL与碘的不同同位素进行 确定激素治疗对合成的影响 Apo-B的分解代谢。 确定雌激素和孕激素的作用 在LDL去除途径上，修饰LDL的周转研究（环己二酮 用I131标记的LDL处理的LDL和未修饰的LDL（用I125标记）将 进行。 同样，确定女性治疗的影响 性激素关于apo-e和apo-a-i的合成和去除，营业额 研究将在碘化孤立的载蛋白和 将它们掺入脂蛋白（VLDL和HDL）中。 动力学数据将 可以通过建模来分析。 性类固醇激素的影响也将是 研究了育儿蛋白血浆脂蛋白脂肪酶和肝甘油三酸酯的研究 脂肪酶活性和甘油三酸酯分泌。 我们将进一步确定是否 脂蛋白代谢参数的变化是由肝介导的 通过测量治疗和 未经处理的动物。 最后，脂蛋白模式的影响改变了 雌激素，孕酮或组合 将研究动脉粥样硬化。 动物将保持在荷尔蒙上 治疗18个月，之后它们将被尸检和动脉。 将测量病变。