SEX STEROID MODULATION OF HUMAN LIPOPROTEIN METABOLISM

人类脂蛋白代谢的性类固醇调节

• 批准号: 3354333
• 负责人: WILLIAM R HAZZARD
• 金额: $ 14.07万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-06-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3354333
• 关键词: androgens; apolipoproteins; blood lipid; blood lipoprotein metabolism; electrofocusing; estrogens; familial hyperlipoproteinemia type II; familial hyperlipoproteinemia type III; female; gel filtration chromatography; gender difference; high density lipoproteins; hormone regulation /control mechanism; hormone therapy; human subject; lipoprotein disorder; lipoprotein lipase; low density lipoprotein; mathematical model; radioimmunoassay; receptor; steroid hormone; triacylglycerol lipase; ultracentrifugation; very low density lipoprotein

To probe the mechanism of the sex differential in lipoprotein metabolism (and in turn the sex differential in atheroslcerosis and indeed longevity itself in Occidental societies), exogenous estrogen (ethinyl estradiol [EE], 1 mcg/kg/d) or androgen (stanozolol [Sz], 6 mg/d) will be administered to normolipidemic post-menopausal and dyslipoproteinemic women. Paired studies of plasma lipids, lipoproteins (VLDL, IDL, LDL, HDL2, HDL3), apolipoproteins (A-I, A-II, B-100, E) post-heparin hepatic triglyceride lipase (HTGL) and lipoprotein lipase (LPL), radio-iodinated apolipoprotein turnover (VLDL apo-B, apo-E, apo-A-I and A-II) will be performed before and during sex steroid treatment on a metabolic isocaloric diet of 40% F, 45% CHO, 15% P, P/S 0.8, cholesterol 450 mg/d. Multicompartmental mathematical modelling will be performed to analyze the regulation of lipoprotein metabolism in the basal state and its modulation by estrogen and androgen using results of steady state tracer studies to constrain modeling of non-steady state unlabeled lipid, lipoprotein, and post-heparin triglyceride lipase data. Additional insights will be afforded by similar studies of sex steroid effects on LDL subfraction kinetics, the catabolism of cyclohexanedione-modified vs. unmodified LDL (to examine LDL-receptor vs. scavenger pathways), and parallel studies of women with well-characterized dyslipoproteinemias, notably hyperapobetalipoproteinemia of homozygous apo-E2 phenotype (Type III hyperlipoproteinemia) or of other apo-E phenotypes (and Types IIa, IIb, or IV lipoprotein patterns) and women with LDL-receptor deficiency (familial hypercholesterolemia, homozygous or heterozygous).

探讨脂蛋白代谢性别差异的机制 (and动脉粥样硬化和寿命的性别差异 本身在西方社会），外源性雌激素（炔雌醇 [EE]，1 mcg/kg/d）或雄激素（司坦唑醇[Sz]，6 mg/d） 给药于绝经后血脂正常和血脂异常的患者 妇女 对血浆脂质、脂蛋白（VLDL、IDL、LDL、LDL、LDL、LDL） HDL 2、HDL 3）、载脂蛋白（A-I、A-II、B-100、E）肝素后肝 放射性碘标记甘油三酯脂肪酶和脂蛋白脂肪酶 载脂蛋白周转率（VLDL apo-B、apo-E、apo-A-I和A-II）将 在性类固醇治疗之前和期间进行代谢等热量 日粮为40%F、45%CHO、15%P，P/S为0.8，胆固醇为450 mg/d。 将进行多房室数学建模，以分析 基础状态下脂蛋白代谢的调节及其调节 雌激素和雄激素使用稳态示踪研究的结果， 非稳态未标记脂质、脂蛋白和 肝素后甘油三酯脂肪酶数据。 其他见解将是 性类固醇对LDL亚组分影响的类似研究提供了 动力学，环己二酮修饰与未修饰LDL的催化剂 (to检查LDL受体与清除剂途径），以及 具有明确特征的异常脂蛋白血症的女性，特别是 纯合子apo-E2表型高apo-beta脂蛋白血症（III型 高脂蛋白血症）或其他apo-E表型（和IIa、IIb或 IV脂蛋白模式）和女性LDL受体缺乏症（家族性 高胆固醇血症，纯合子或杂合子）。