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Research Article Free access | 10.1172/JCI114552

Feedback regulation of bile-acid synthesis in the rat. Differing effects of taurocholate and tauroursocholate.

S Shefer, L Nguyen, G Salen, A K Batta, D Brooker, F G Zaki, I Rani, and G S Tint

Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103.

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Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103.

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Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103.

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Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103.

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Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103.

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Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103.

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Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103.

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Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103.

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Published April 1, 1990 - More info

Published in Volume 85, Issue 4 on April 1, 1990
J Clin Invest. 1990;85(4):1191–1198. https://doi.org/10.1172/JCI114552.
© 1990 The American Society for Clinical Investigation
Published April 1, 1990 - Version history
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Abstract

We studied the effect of the orientation of the 7-hydroxyl group in taurocholate (7 alpha) and tauroursocholate (7 beta) on the feedback regulation of bile-acid synthesis and its rate-controlling enzyme, cholesterol 7 alpha-hydroxylase, in bile-fistula rats. To ensure a constant supply of cholesterol and to label newly synthesized bile acids, RS[2-14C]mevalonolactone was infused intraduodenally at 154 mumol/h before and during bile-acid infusion. Mevalonolactone inhibited hydroxymethyl-glutaryl CoA reductase activity 90% but did not increase bile-acid synthesis and cholesterol 7 alpha-hydroxylase activity. When sodium taurocholate was infused at the rate of 27 mumol/100 g rat per h (equivalent to the hourly hepatic bile-acid flux), bile-acid synthesis decreased 82% and cholesterol 7 alpha-hydroxylase activity declined 78%. This inhibitory effect was observed in the absence of hepatic damage. In contrast, sodium tauroursocholate infused at the same rate did not decrease bile-acid synthesis nor cholesterol 7 alpha-hydroxylase activity. Hepatic cholesterol content rose 36% with sodium taurocholate but did not change during sodium tauroursocholate administration. These results demonstrate that the feedback inhibition of bile-acid synthesis is mediated through the regulation of cholesterol 7 alpha-hydroxylase. In these experiments, taurocholate was a far more potent inhibitor than its 7 beta-hydroxy epimer, tauroursocholate.

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