SEX STEROID MODULATION OF HUMAN LIPOPROTEIN METABOLISM

探讨脂蛋白代谢性别差异的机制

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).