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Ahn, Lee, Kim, Kim, Kang, Lim, Yoon, Kim, Park, Cho, and Park: Effect of Thyroid Hormone to the Expression of Bile Salt Export Pump
Original Article
Endocrinology and Metabolism

Endocrinology and Metabolism 2011; 26(3): 232-238.

Published online: 27 September 2011

DOI: https://doi.org/10.3803/EnM.2011.26.3.232

Effect of Thyroid Hormone to the Expression of Bile Salt Export Pump

Hwa Young Ahn1, 2, Kwan Jae Lee2, Soon Hui Kim1, Eun Ky Kim1, Ah Reum Kang1, Jung Ah Lim1, Ji Won Yoon1, 3, Kyung Won Kim1, 3, Do Joon Park1, Bo Youn Cho4, Young Joo Park1, 2

1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

2Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

3Department of Internal Medicine, Seoul National University, Healthcare System, Seoul, Korea.

4Department of Internal Medicine, Chung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul, Korea.

Corresponding author: Young Joo Park. Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea. Tel: +82-2-2072-4183, Fax: +82-2-764-2199, yjparkmd@snu.ac.kr

Received 13 June 2011       Accepted 22 July 2011

Copyright © 2011 Korean Endocrine Society

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Bile acids were important for the regulation of cholesterol homeostasis. Thyroid hormone increased the expression of CYP7A1 (cholesterol 7α-hydroxylase), catalyzing the first step in the biosynthesis of bile acids. However, the effect of thyroid hormone on bile acid export has not been previously assessed. The principal objective of this study is to evaluate the effects of thyroid hormone on the bile salt export pump (BSEP).

Methods

Thyroid hormone, T3 (1 mg/g) was administered to male mice via intraperitoneal injection. After 6 hours and 5 days of T3 treatment, we measured serum total and LDL cholesterol and hepatobiliary bile acid concentrations. We assessed the changes associated with bile acid synthesis and transport. In order to evaluate the direct effect of thyroid hormone, we assessed the changes in the levels of BSEP protein after T3 administration in human hepatoma cells.

Results

Serum total and LDL cholesterol were reduced and hepatobiliary bile acid concentrations were increased following T3 treatment. Expressions of Cyp7a1 and BSEP mRNA were increased following T3 treatment. The levels of the BSEP protein in the mouse liver as well as in the human hepatoma cells were increased after T3 treatment.

Conclusion

Thyroid hormone can regulate LDL cholesterol metabolism. It increases bile acid synthesis and the excretion of bile acids via increased BSEP expression.

Keywords: Bile acids, Cholesterol, Thyroid hormone

Figures and Tables

Fig. 1
Genes related to bile acid synthesis and transport in hepatocyte. BSEP, bile salt export pump; CYP7A1, cholesterol 7α hydroxylase; CYP27A1, sterol 27 hydroxylase; CYP8B1, sterol 12α hydroxylase; MRP, multidrug-resistance associated protein; NTCP, Na-dependent taurocholate cotransport peptide; OATP, organic anion transporting polypeptide.
enm-26-232-g001
Fig. 2
Effect of thyroid hormone to serum cholesterol (A), LDL cholesterol (B) and hepatobiliary bile acid (C) level. LDL, low density lipoprotein; T3, 3,5,3'-triiodo-L-thyronine (thyroid hormone).
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Fig. 3
Effect of thyroid hormone to Cyp7a1, BSEP and MRP2 expression. Cyp7a1 and BSEP mRNA expression of mouse liver were increased after T3 treatment in northern blot analysis (A), MRP2 mRNA expression of mouse liver after 5 days of T3 treatment did not change in RT-PCR analysis (B), protein level of BSEP in mouse liver was also increased after 5 days of T3 treatment in western blot analysis (C). Cyp7a1, cholesterol 7α hydroxylase; BSEP, bile salt export pump; MRP2, -resistance associated protein 2; RT-PCR, reverse transcriptase polymerase chain reaction; T3, 3,5,3'-triiodo-L-thyronine (thyroid hormone).
enm-26-232-g003
Fig. 4
Effect of thyroid hormone to protein levels of BSEP. Protein levels of BSEP were increased after T3 treatment in human hepatoma cells. BSEP, bile salt export pump; T3, 3,5,3'-triiodo-L-thyronine (thyroid hormone).
enm-26-232-g004
Table 1
Differentially expressed genes involved in bile acid synthesis and transport in mouse hepatocytes after thyroid hormone treatment
enm-26-232-i001

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