Effect of estrogen and progesterone on metabolism of apoprotein B in baboons.

To determine the metabolic mechanisms by which estrogen and progesterone alter levels of apoprotein B (apo B)-containing lipoproteins, 12 ovariectomized and hysterectomized baboons, maintained on a high-cholesterol (1.7 mg/kcal) and a high-fat (40% from lard) diet and divided into four groups, were treated with estrogen, progesterone, estrogen plus progesterone, and a placebo. After 12 wk, plasma cholesterol was unchanged in the control and progesterone groups but was reduced in the estrogen- and estrogen plus progesterone-treated groups. The reduction was primarily because of decreased low-density lipoprotein (LDL) cholesterol. LDL apo B levels decreased parallel to the LDL cholesterol. Very low-density lipoprotein (VLDL) and LDL apo B metabolism were studied using a double-label turnover study. Multicompartmental modeling suggested that LDL apo B was kinetically heterogeneous and that there exists an extravascular pool, perhaps consisting of hepatic remnants, that contributes significantly to LDL apo B transport. The model was used to estimate apo B production rates and residence times. VLDL apo B production was not affected by estrogen but was increased by progesterone. LDL apo B production was increased by both estrogen and progesterone. The residence time of LDL apo B was decreased by estrogen and estrogen plus progesterone but not by progesterone. Thus estrogen and progesterone have independent effects on apo B metabolism in baboons.