Effect of naturally reduced ovarian function on plasma lipoprotein and 27-hydroxycholesterol levels in baboons ( Papio sp.)

Abstract

Female baboons over 15 years of age develop irregular menstrual cycles, an indication of declining ovarian function similar to that occurring in perimenopausal women. To determine the effect of declining ovarian function on plasma lipoprotein metabolism and plasma oxysterols, we measured plasma lipoprotein and 27-hydroxycholesterol levels in 86 female baboons from 15–28 years of age with regular ( n=51) and irregular ( n=35) menstrual cycles. We sampled blood and liver while they were consuming a basal diet and after consuming a high cholesterol and high fat diet for 7 weeks. On the basal diet, baboons with irregular cycles had higher VLDL+LDL/HDL cholesterol ratios ( P=0.034). After consuming the HCHF diet for 7 weeks, total plasma ( P<0.001) and VLDL+LDL ( P<0.001) cholesterol concentrations and VLDL+ LDL/HDL sterol ratios ( P<0.001) increased in both cycle groups; whereas HDL cholesterol concentrations increased only in baboons with regular cycles ( P=0.009). As a result, HDL cholesterol concentrations ( P=0.006) were lower and VLDL+LDL/HDL cholesterol ratios ( P=0.002) were higher in baboons with irregular cycles on the HCHF diet. Plasma 27-hydroxycholesterol concentrations were higher in baboons with regular cycles than in those with irregular cycles on both basal ( P=0.018) and HCHF ( P=0.037) diets and were positively correlated ( P<0.001) with hepatic sterol 27-hydroxylase activities on both diets. Hepatic sterol 27-hydroxylase activities were negatively correlated with the VLDL+LDL/HDL cholesterol ratios on the HCHF diet ( r= −0.342, P=0.033). These results suggest that declining ovarian function changes the plasma lipoprotein pattern to one that is more atherogenic. Ovarian failure is also associated with decreased concentrations of plasma 27-hydroxycholesterol (the major oxysterol of plasma), and the decrease in plasma 27-hydroxycholesterol concentration was due to the decrease in hepatic sterol 27-hydroxylase activity. The effects of ovarian failure on plasma lipoprotein metabolism and plasma 27-hydroxycholesterol may be mediated by the decreased production of estrogen in perimenopausal baboons. Thus, the perimenopausal baboon is an excellent model for menopause and can be used for studies that cannot be conducted in women.