Gastric Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Aug 7, 2006; 12(29): 4640-4645
Published online Aug 7, 2006. doi: 10.3748/wjg.v12.i29.4640
Suppression of bile acid synthesis by thyroid hormone in primary human hepatocytes
Ewa Cristine Siljevik Ellis
Ewa Cristine Siljevik Ellis, Department of Medicine, Division of Gastroenterology and Hepatology, and the Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska University Hospital at Huddinge, Karolinska Institute, Stockholm, Sweden
Supported by the Swedish Research Council, the Karolinska Institute and the Swedish Society for Medical Research
Correspondence to: Dr. Ewa Cristine Siljevik Ellis, Department of Pathology, University of Pittsburgh, 200 Lothrop Street, Biomedical Science Tower S-450, Pittsburgh, PA 152 61, United States. ece5@pitt.edu
Telephone: +1-412-6241309 Fax: +1-412-3837969
Received: October 4, 2005
Revised: October 28, 2005
Accepted: November 10, 2005
Published online: August 7, 2006
Abstract

AIM: It is known that thyroid hormones alter the bile acid metabolism in humans, however the effect on individual enzymes has been difficult to elucidate. This is mainly due to the lack of human liver cell lines producing bile acids. We used cultures of primary human hepatocytes to study the effects of triiodothyronine (T3) on bile acid synthesis.

METHODS: Primary hepatocytes were isolated from liver tissue obtained from three different patients undergoing liver resection due to underlying malignancy. The hepatocytes were cultured under serum-free conditions and treated from d 1 to d 5 with culture containing 0.1 - 1000 nmol/L of T3. Bile acid formation and mRNA levels of key enzymes were analysed.

RESULTS: The lowest concentration of T3 decreased cholic acid (CA) formation to 43%-53% of controls and chenodeoxycholic acid (CDCA) to 52%-75% of controls on d 5. The highest dose further decreased CA formation to 16%-48% of controls while CDCA formation remained at 50%-117% of controls. Expression of mRNA levels of cholesterol 7α-hydroxylase (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) dose-dependently decreased. Sterol 27-hydroxylase (CYP27A1) levels also decreased, but not to the same extent.

CONCLUSION: T3 dose-dependently decreased total bile acid formation in parallel with decreased expression of CYP7A1 and CYP8B1. CA formation is inhibited to a higher degree than CDCA, resulting in a marked decrease in the CA /CDCA ratio.

Keywords: Hepatocytes; Human; Bile acids; CYP7A1; CYP8B1; CYP27A1