Estrogen increases low-density lipoprotein receptor-independent catabolism of apolipoprotein B in hyperlipidemic rabbits

Estrogen has been reported to increase the catabolism of low-density lipoprotein (LDL) apolipoprotein (apo) B by increasing LDL receptor activity. To determine the effect of estrogen on LDL receptor-independent pathways, paired turnover studies of native LDL and chemically modified LDL (methyl-LDL) were performed before and during estrogen administration in female New Zealand rabbits consuming a diet containing 0.5% (wt/wt) cholesterol. Rabbits were matched by plasma cholesterol concentration and assigned randomly to receive estrogen (estradiol cypionate 0.5 mg/kg/wk) or placebo. The residence time of both the native LDL apo B tracer and the methyl-LDL apo B tracer in plasma was decreased by estrogen but not by placebo. Multicompartmental modeling of the paired, double-labeled turnover studies indicated that an increase in fractional catabolic rate (FCR) of the fast-turnover pool, a kinetically distinct LDL subpopulation in plasma, accounted for the observed decrease in residence time in plasma for both tracers. These data support the hypothesis that, in addition to any effect on the LDL receptor, estrogen promotes the activity of LDL receptor-independent pathways.