Endocrinol Metab.  2011 Sep;26(3):232-238. 10.3803/EnM.2011.26.3.232.

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

• Ahn HY
• Lee KJ
• Kim SH
• Kim EK
• Kang AR
• Lim JA
• Yoon JW
• Kim KW
• Park DJ
• Cho BY
• Park YJ

• KMID: 2169174
• DOI: http://doi.org/10.3803/EnM.2011.26.3.232

Abstract

BACKGROUND
Bile acids were important for the regulation of cholesterol homeostasis. Thyroid hormone increased the expression of CYP7A1 (cholesterol 7alpha-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.

Keyword

Bile acids; Cholesterol; Thyroid hormone

MeSH Terms

Animals
Bile
Bile Acids and Salts
Carcinoma, Hepatocellular
Cholesterol
Cholesterol, LDL
Homeostasis
Humans
Injections, Intraperitoneal
Liver
Male
Mice
Resin Cements
RNA, Messenger
Thyroid Gland
Triiodothyronine
Bile Acids and Salts
Cholesterol
Cholesterol, LDL
RNA, Messenger
Resin Cements
Triiodothyronine

Figure

• 

  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.

• 

  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).

• 

  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).

• 

  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).

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