Mechanisms of gallstone formation in women. Effects of exogenous estrogen (Premarin) and dietary cholesterol on hepatic lipid metabolism.
Open Access
- 1 January 1991
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 87 (1), 237-246
- https://doi.org/10.1172/jci114977
Abstract
Our aim was to define mechanisms whereby conjugated estrogens (Premarin, exogenous estrogen; Ayerst Laboratories, New York) increase the risk of developing cholesterol gallstones and to determine the role, if any, of dietary cholesterol. We studied gallbladder motor function, biliary lipid composition and secretion, cholesterol absorption, cholesterol synthesis and esterification by peripheral blood mononuclear cells, the clearance of chylomicron remnants, and bile acid kinetics in 29 anovulatory women. 13 were studied on both a low (443 +/- 119 mumol/d) and high (2,021 +/- 262 mumol/d) cholesterol diet. Premarin increased the lithogenic index of bile (P less than 0.05), increased biliary cholesterol secretion (P less than 0.005), lowered chenodeoxycholate (CDCA) pool (P less than 0.001) and synthesis (P less than 0.05), altered biliary bile acid composition [( CA + DCA]/CDCA increases, P less than 0.005), stimulated cholesterol esterification (P less than 0.03), and enhanced the clearance of chylomicron remnants (P = 0.07). Increases in dietary cholesterol stimulated the biliary secretion of cholesterol (P = 0.07), bile acid (P less than 0.05), phospholipid (P = 0.07), and as a result, did not alter lithogenic index. The reduction in CDCA pool and synthesis by Premarin was reversed by increasing dietary cholesterol. Off Premarin, only 24% of the increase in cholesterol entering the body in the diet was recovered as biliary cholesterol or newly synthesized bile acid. On Premarin, 68% of this increase in cholesterol was recovered as these biliary lipids. We conclude that Premarin increases biliary cholesterol by enhancing hepatic lipoprotein uptake and inhibiting bile acid synthesis. These actions of Premarin divert dietary cholesterol into bile.Keywords
This publication has 55 references indexed in Scilit:
- Contraceptive steroids increase hepatic uptake of chylomicron remnants in healthy young women.Journal of Lipid Research, 1988
- Effects of acute changes of bile acid pool composition on biliary lipid secretion.JCI Insight, 1984
- The effect of a progestin on gallbladder function in young womenAmerican Journal of Obstetrics and Gynecology, 1984
- Plasma lipoprotein retinoids after vitamin A feeding in normal man: Minimal appearance of retinyl esters among low-density lipoproteinsMetabolism, 1983
- Bile acid secretion by cultured rat hepatocytes. Regulation by cholesterol availability.Journal of Biological Chemistry, 1983
- Effect of synthetic oestrogens and progestagens in oral contraceptives on bile lipid composition.Gut, 1983
- A Physiological Method for Estimation of Hepatic Secretion of Biliary Lipids in ManGastroenterology, 1972
- Effects of dietary cholesterol on the regulation of total body cholesterol in manJournal of Lipid Research, 1971
- The epidemiology of gallbladder disease: Observations in the Framingham studyJournal of Chronic Diseases, 1966
- Phosphorus Assay in Column ChromatographyJournal of Biological Chemistry, 1959