SEX STEROID MODULATION OF HUMAN LIPOPROTEIN METABOLISM

人类脂蛋白代谢的性类固醇调节

• 批准号: 3354335
• 负责人: WILLIAM R HAZZARD
• 金额: $ 8.59万
• 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/3354335
• 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; 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).

探讨脂蛋白代谢中性别差异的机制 (反过来，动脉粥样硬化症和长寿方面的性别差异 在西方社会中)，外源性雌激素(乙炔雌二醇 [EE]，1微克/公斤/天)或雄激素(司坦唑醇[Sz]，6毫克/天) 用于绝经后血脂正常和血脂异常的患者 女人。血脂、脂蛋白(极低密度脂蛋白、 HDL2、HDL3)、载脂蛋白(A-I、A-II、B-100、E) 放射性碘化甘油三酯脂肪酶(HTGL)和脂蛋白脂肪酶(LPL) 载脂蛋白周转率(极低密度脂蛋白载脂蛋白B、载脂蛋白E、载脂蛋白A-I和载脂蛋白A-II) 代谢性等卡路里患者在性激素治疗前和治疗期间进行的检查 日粮为40%F、45%CHO、15%P，P/S 0.8，胆固醇450 mg/d。 将进行多间隔数学建模，以分析 基础状态下脂蛋白代谢的调节及其调控 通过雌激素和雄激素使用稳态示踪研究的结果来 非稳态未标记脂质、脂蛋白和 肝素后甘油三酯脂肪酶数据。更多的见解将是 由性激素对低密度脂蛋白亚组分影响的类似研究提供 环己二酮修饰低密度脂蛋白与未修饰低密度脂蛋白的分解代谢动力学 (研究低密度脂蛋白受体与清道夫途径)，以及平行研究 具有良好特征的血脂异常的妇女，值得注意的是 Apo-E2纯合子表型(III型)的高脂蛋白血症 高脂蛋白血症)或其他载脂蛋白E表型(以及IIa、IIb或 IV脂蛋白模式)与低密度脂蛋白受体缺乏的妇女(家族性 高胆固醇血症，纯合子或杂合子)。