Effect of Pregnancy on Bile Flow and Biliary Lipids in the Hamster

Abstract

The administration of estrogens and oral contraceptive steroids containing estrogen and a progestogen affects biliary lipids, bile acids, and bile flow in a number of animal species. The physiologic relevance of these observations has been examined in the hamster by studying hepatobiliary function in pregnancy, a state characterized by high levels of estrogens and progesterone. The rate of bile flow and the excretion of biliary lipids were studied on the 9th and 14th days of pregnancy and compared with those of nonpregnant females and males of similar ages. The authors measured the concentration, composition, and secretion of bile acids, phospholipids, and cholesterol in hepatic bile. There were no differences in these measurements between males and nonpregnant females. In pregnant females, the following changes were observed: (a) a progressive fall in bile flow, which in late pregnancy (14th day) was decreased 62%; the decrease in bile flow (67%) was principally in the bile acid-independent fraction; (b) reduced secretion of total bile acids due to decreased cholic acid secretion; the decreased output of bile acid, especially cholic acid, may reflect a reduced pool size during pregnancy; (c) increased concentration of biliary lipids but no significant change in the lithogenic index of bile; and (d) the appearance of β-muricholic and hydodeoxycholic acids in the bile. In addition, (Na+K+)ATPase activity was reduced but (Mg++)ATPase activity was not altered in liver homogenates of 14-day pregnant animals. These effects of pregnancy—decreased bile acid-independent bile flow, decreased hepatic (Na+K+)ATPase activity, and decreased cholic acid secretion—are similar to those produced by estrogen administration in hamsters and rats. The findings stress the importance of changes in hepatobiliary function produced by female sex hormones in an important physiologic state.