EFFECT OF ESTRADIOL AND PROGESTERONE ON CHOLESTEROL 7-ALPHA-HYDROXYLASE ACTIVITY IN RATS SUBJECTED TO DIFFERENT FEEDING CONDITIONS

The regulation of cholesterol 7 alpha-hydroxylase activity by estradio l 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. Differential ef fects were observed when the direct action of estradiol and progestero ne an microsome preparations was examined. Cholesterol 7 alpha-hydroxy lase 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 mu M estradiol induced small and selective 7 alpha-hydroxylase increas es in fasting and cholestyramine fed animals, then activity declined t o central values and consistent decreases were found from 20 mu M. The administration of estradiol (50 mu g) or progesterone (100 mu g) for 21 days resulted in depressed cholesterol 7 alpha-hydroxylase activity in rats with high bile acid synthesis basal Fate clue to cholestyrami ne feeding. In rats receiving a standard diet, either an libitum or af ter 24 h fasting, the hormonal effects did not reach significance. Dec lines in the content of free cholesterol were provoked by progesterone , not by estradiol, in liver microsomes prepared from all feeding grou ps. No changes in cholesterol 7 alpha-hydroxylase activity and microso mal free cholesterol were observed after administration of the sex hor mones for 3 days. Rapid and transient inhibitions in 7 alpha-hydroxyla se activity were found after the single injection of progesterone to f ed animals. Estradiol, on the contrary, was unable to alter rapidly th e hepatic 7 alpha-hydroxylase capacity. It is concluded that: i) estra diol and progesterone act directly on liver microsome membranes inhibi ting the activity of cholesterol 7 alpha-hydroxylase, ii) changes in t he dietary conditions are important in the in vivo regulation of 7 alp ha-hydroxylase by these hormones, and iii) progesterone appears to be an inhibitor of cholesterol 7 alpha-hydroxylase more potent than estra diol.