The effects of estrogen administration (ethinyl estradiol; 0.1 mg, orally, daily) on plasma lipoprotein metabolism were investigated in five normolipidemic premenopausal females. Estrogen administration resulted in significant (P less than 0.05) mean increases in plasma cholesterol, triglyceride, very low density lipoprotein (VLDL)-cholesterol, and high density lipoprotein (HDL)-cholesterol of 18.8%, 87.0%, 123.1%, and 38.3%, respectively. Analytical ultracentrifugation demonstrated that HDL increases occurred mainly in the HDL2b subfraction (150.0% increase). Lipoprotein compositional analysis showed that estrogen administration caused significant increases in all VLDL and HDL constituents (protein, cholesterol, phospholipid, and triglyceride) as well as VLDL apolipoprotein (apo) B (118.9% increase) and HDL apoA-I (27.4% increase). No significant changes in LDL constituents were noted. Measurement of lipoprotein lipase and hepatic lipase enzymic activity in post-heparin plasma revealed no major change in lipoprotein lipase activity, but showed a significant decrease (43.8%) in hepatic lipase activity during estrogen administration. Radioiodinated VLDL and HDL kinetic data indicated increased VLDL apoB (86.1% rise) and HDL apoA-I (24.9% rise) synthesis during estrogen administration. These data are consistent with the concept that estrogen administration at the dose level studied in premenopausal females causes significant elevations in VLDL and HDL constituents, associated with enhanced production of VLDL apoB and HDL apoA-I.

To define the metabolic defect in Tangier disease, we studied the kinetics of [125I]-high-density lipoprotein apolipoproteins (apolipoproteins A-I and A-II) in 11 normal subjects, two obligate heterozygotes, and two homozygotes. Mean synthesis of apolipoproteins A-1 and A-11 was 8.24 mg per kilogram per day in the normal group, 7.94 in heterozygotes and 3.66 in homozygotes. The mean plasma-residence time for both apolipoproteins was 5.21 days in the normal subjects, 3.41 days in heterozygotes, and 0.52 days in homozygotes. In normal subjects and heterozygotes the apolipoproteins were catabolized at similar rates, whereas in homozygotes apolipoprotein A-I was catabolized at a much greater fractional rate than apolipoprotein A-II. These findings indicate that the deficiency of these apolipoproteins in Tangier disease is largely due to rapid and altered catabolism.

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