Y. Chico et al., EFFECT OF ESTRADIOL AND PROGESTERONE ON CHOLESTEROL 7-ALPHA-HYDROXYLASE ACTIVITY IN RATS SUBJECTED TO DIFFERENT FEEDING CONDITIONS, Steroids, 59(9), 1994, pp. 528-535
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.