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 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. Differential effects were observed when the direct action of estradiol and progesterone on microsome preparations was examined. Cholesterol 7 alpha-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 microM estradiol induced small and selective 7 alpha-hydroxylase increases in fasting and cholestryamine-fed animals, then activity declined to control values and consistent decreases were found from 20 microM. The administration of estradiol (50 micrograms) or progesterone (100 micrograms) for 21 days resulted in depressed cholesterol 7 alpha-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 7 alpha-hydroxylase activity and microsomal free cholesterol were observed after administration of the sex hormones for 3 days. Rapid and transient inhibitions in 7 alpha-hydroxylase activity were found after the single injection of progesterone to fed animals. Estradiol, on the contrary, was unable to alter rapidly the hepatic 7 alpha-hydroxylase capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, University of the Basque Country Medical School, Bilbao, Spain.
Y
Y
Chico
O
O
Fresnedo
M
M
Lacort
B
B
Ochoa
D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis; D002784:Cholesterol / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000187:drug effects*; D002792:Cholestyramine Resin / Q000008:administration & dosage*; D004032:Diet; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013217:Starvation / Q000201:enzymology*
D001647:Bile Acids and Salts; D002792:Cholestyramine Resin; D011374:Progesterone; D004958:Estradiol; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase