Effects of estradiol, dietary cholesterl and 1-thyroxine on biliary bile acid composition and secretory rate, and on plasma, liver and bile cholesterol levels in rats.

Abstract

Biliary bile acid composition and secretory rate, as well as cholesterol concentra tions in plasma, liver and bile, were investigated in rats given estradiol for 3 days and for 3 weeks, a 2% cholesterol supplemented diet for 4 to 8 weeks, and 1-thyroxine for a week, in order to ascertain the relations between cholesterol concentrations in tissues and bile acid production.Biliary samples collected from control rats during the first 2 hrs. period of can nulation contained 11 mg bile acid per ml of biliary samples on an average, consisting of 69% cholic acid, 7% hyodeoxycholic acid, 6% deoxycholic acid, 6%α-muricholic acid, 5% chenodeoxycholic acid, 3% unidentified acid and minor percentages of lithocholic acid, two other unidentified acids, 7-oxo-lithocholic acids. A 3-day treatment with estradiol caused a decrease in plasma cholesterol and an increase in liver cholesterol, but a 3-week treatment with this steroid significantly increased the plasma cholesterol level. Either acute or chronic estradiol treatment caused an increase in chenodeoxycholic acid and its further converted bile acids in the bile. When rats were fed the cholesterol diet for several weeks, increases in chenodeoxycholic, hyodeoxycholic, α-muricholic and lithocholic acids with a concomitant decrease in cholic acid were observed, and this was accompa nied with a slight increase of cholesterol in the liver (30%) and plasma (10%). Both liver and plasma cholesterol levels were markedly elevated by giving cholesterol and sodium cholate simultaneously. 1-Thyroxine treatment caused no change in plasma cholesterol level but increased chenodeoxycholic acid formation to provide a biliary bile acid com position similar to that of the rats treated with estradiol or cholesterol dietThese data suggest that the treatment with either estradiol or cholesterol diet, as well as the treatment with 1-thyroxine, increases chenodeoxycholic acid formation. The increase of chenodeoxycholic acid formation appears to be related to an increase in the liver cholesterol level but not to the change in the plasma cholesterol level. A defence mechanism for alimentary hypercholesterolemia in the rat was discussed on the basis of chenodeoxycholic acid formation.