Contraceptive steroids increase hepatic uptake of chylomicron remnants in healthy young women

Abstract

In an investigation of alterations in cholesterol metabolism during contraceptive steroid use, we studied plasma clearance of chylomicron remnants. Six healthy women were studied on and off contraceptive steroid therapy. Remnant clearance was measured from the disappearance of retinyl palmitate administered intravenously in plasma endogenously labeled with retinyl palmitate. We also measured cholesterol in HDL and its subfractions and postheparin lipoprotein lipase and hepatic triglyceride lipase activities. Plasma decay of retinyl palmitate was biexponential. The rapid component, reflecting chylomicron remnant removal, accounted for about 90% of the total clearance in all studies. During contraceptive steroid intake, both rapid and slow decay constants and the calculated plasma clearance rates were significantly increased (mean values: rapid decay constant, control 0.048 versus treated 0.101 min-1, P less than 0.05; slow decay constant, 0.004 versus 0.014 min-1, P less than 0.01; plasma clearance 74 versus 115 ml/min, P less than 0.025) indicating enhanced hepatic uptake of chylomicron remnants and probably an increased hepatic uptake of higher density lipoproteins (d greater than 1.006 g/ml). Total postheparin lipolytic activity and lipoprotein lipase activity were depressed in all six women (P less than 0.05) and hepatic triglyceride lipase activity was increased in four of five subjects. Contraceptive steroids also caused a decrease in the HDL2/HDL3 cholesterol ratio (P less than 0.05), implying impaired peripheral lipoprotein triglyceride hydrolysis and/or increased HDL2 clearance by hepatic triglyceride lipase. In conclusion, during intake of contraceptive steroids, the plasma clearance of chylomicron remnants and higher density lipoproteins was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: This study analyzed the effect of contraceptive steroids on plasma clearance of chylomicron remnants, the major carrier of exogenous cholesterol to the liver. Autologous plasma containing chylomicrons endogenously labeled with retinyl palmitate was used to estimate chylomicron remnant clearance in the 6 study subjects. During contraceptive steroid intake, both rapid and slow decay constants and the calculated plasma clearance rates were significantly increased over periods of nonintake, indicating enhanced hepatic uptake of chylomicron remnants and probably an increased hepatic uptake of higher density lipoproteins (HDL). Total postheparin lipolytic activity and lipoprotein lipase activity were depressed in all 6 subjects and hepatic triglyceride lipase activity was increased in 4 subjects. Contraceptive steroids further caused a decrease in the HDL2/HDL3 cholesterol ratio, implying impaired peripheral lipoprotein triglyceride hydrolysis and/or increased HDL2 clearance by hepatic triglyceride lipase. The increase in plasma clearance of retinyl palmitate were significantly greater in the 4 women taking steroids containing mestranol than in the 2 women taking ethinyl estradiol preparations. Since contraceptive steroids appear to stimulate receptor-mediated pathways for hepatic cholesterol uptake, the hepatic metabolism of cholesterol is also likely to be altered.