Effect of estradiol and progesterone on cholesterol 7α-hydroxylase activity in rats subjected to different feeding conditions

Abstract

The regulation of cholesterol 7α-hydroxylase activity by estradiol and progesterone was investigated in liver microsomes isolated from rats fed standard diet, either ad libitum or fasted for 24 h, and diet containing the bile acid sequesterant cholestyramine. Differentieffects were observd when the direct action of estradiol and progesterone on microsome preparations was examined. Cholesterol 7α-hydroxylase activity was inhibited by progesterone in a dose-dependent way to almost complete abolition; similar patterns of declines were found in the three feeding groups under study. In contrast, the addition of 5 μM estradiol induced small and selective 7α-hydroxylase increases in fasting and cholestyramine-fed animals, then activity declined to control values and consistent decreases were found from 20 μM. The administration of estradiol (50 μg) or progesterone (100 μg) for 21 days resulted in depressed cholesterol 7α-hydroxylase activity in rats with high bile acid synthesis basal rate due to cholestyramine feeding. In rats receiving a standard diet, either ad libitum or after 24 h fasting, the hormonal effects did not reach significance. Declines in the content of free cholesterol were provoked by progesterone, not by estradiol, in liver microsomes prepared from all feeding groups. No changes in cholesterol 7α-hydroxylase activity and microsomal free cholesterol were observed after administration of the sex hormones for 3 days. Rapid and transient inhibitions in 7α-hydroxylase activity were found after the single injection of progesterone to fed animals. Estradiol, on the contrary, was unable to alter rapidly the hepatic 7α-hydroxylase capacity. It is concluded that: i) estradiol and progesterone act directly on liver microsome membranes inhibiting the activity of cholesterol 7α-hydroxylase, ii) changes in the dietary conditions are important in the in vivo regulation of 7α-hydroxylase by these hormones, and iii) progesterone appears to be an inhibitor of cholesterol 7α-hydroxylase more potent than estradiol.