Feedback inhibition of bile acid synthesis in cultured pig hepatocytes.
Bile acid synthesis by cultured pig hepatocytes, as measured by conversion of [14C]cholesterol to bile acids, increased during the second and third day of culture. This rise was inhibited after addition of various conjugated and unconjugated bile acids in a concentration of 100 microM. It could be completely prevented by cycloheximide, indicating that de novo protein synthesis is required for the increase in bile acid formation. No effect of exogenous bile salts on LDH release to the medium or on cellular ATP content was observed, demonstrating that hepatocyte viability was not affected. During the period in which bile acid synthesis was inhibited, pig hepatocytes were able to accumulate taurocholic acid (100 microM) up to 7-18 nmol per mg cell protein (decreasing during culture time). It is concluded that feedback regulation of bile acid synthesis is exerted by direct action of bile acids on the hepatocyte.
Gaubius Institute TNO, Leiden, The Netherlands.
J
J
Kwekkeboom
E M
EM
van Voorthuizen
H M
HM
Princen
H J
HJ
Kempen
D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000378:metabolism*; D013552:Swine; D013656:Taurocholic Acid / Q000493:pharmacokinetics
D001647:Bile Acids and Salts; D013656:Taurocholic Acid; D002784:Cholesterol; D003513:Cycloheximide