METABOLIC-REGULATION OF PLASMA APOLIPOPROTEIN-E BY ESTROGEN AND PROGESTERONE IN THE BABOON (PAPIO SP)

Apolipoprotein (apo) E plays an important role in the metabolism of lipoproteins. To determine the effects of estrogen and progesterone on plasma levels and metabolism of apo E, we used 12 ovariectomized baboons fed a cholesterol- and fat-enriched diet. These baboons were divided into four groups and treated with estrogen, progesterone, estrogen + progesterone, and a placebo control. After 10 months, although the lipid levels were not different among the treatment groups, low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratios in the estrogen + progesterone group were significantly lower than those in the control and progesterone groups. Estrogen alone or in combination with progesterone decreased plasma apo Elevels significantly compared with those in the control group. Plasma apo E levels in the progesterone group were similar to those in the control group. In all groups, most (> 60%) of the apo E was present in HDL. HDL apo E concentrations in the estrogen and estrogen + progesterone groups were significantly lower than those in the control and progesterone groups. To determine the metabolic mechanisms of these changes in apo E levels, turnover studies were conducted by injection of iodinated apo E-labeled very-low-density lipoprotein (VLDL) and HDL. Residence times were calculated using multicompartment modeling. Progesterone alone and in combination with estrogen decreased residence times of apo E injected in both HDL and VLDL compared with estrogen alone and control groups. Progesterone alone also increased the apo E production rate compared with other groups. On the other hand, estrogen decreased the production rate of apo E in HDL and VLDL and, in addition, decreased the residence time of VLDL apo E compared with the control group. When estrogen was administered with progesterone, the production rate of apo E was not decreased and was similar to that in the control group. This observation suggests that the effect of estrogen on apo E production is counterbalanced by progesterone. © 1991.