J Korean Thyroid Assoc.  2011 May;4(1):39-46.

Effect of Thyroid Hormone to the Expression of ATP-binding Cassette Transporter ABCG5

• Ahn HY
• Jang JM
• Lee KJ
• Kim SH
• Kim KW
• Park DJ
• Jang HC
• Park YJ

Abstract

BACKGROUND AND OBJECTIVES
Excretion of bile acid and free cholesterol of bile was important to maintain cholesterol homeostasis. ATP-binding cassette transporter G5 (ABCG5) and G8 (ABCG8) promoted biliary cholesterol excretion. In previous study, hepatic secretion of cholesterol and ABCG5/G8 expression are strongly stimulated in hypophysectomized rats during treatment with thyroid hormone. In this study, we aimed to evaluate the effect of thyroid hormone to expression of ABCG5 and G8 in mouse liver.
MATERIALS AND METHODS
We administered thyroid hormone (T3) to C57BL/6 mice and then RNA and protein was isolated from liver. We isolated primary hepatocyte and administered T3 to evaluate in vitro effect. HepG2 cells were cotransfected with either a control plasmid or expression plasmids for human thyroid hormone receptor (hTR)beta/human retinoid X receptor (hRXR)alpha or human liver X receptor (hLXR)alpha in combination with reporter plasmids TK-LXRE3-LUC with or without T3.
RESULTS
Serum total cholesterol was decreased after 5 days of T3 treatment. Expression of ABCG5/8 mRNA and ABCG5 protein was increased after T3 treatment. In primary hepatocytes, T3 also increased ABCG5/8 mRNA expression. LXRalpha mRNA was not increased by T3. However, when we cotransfected liver X receptor response element (LXRE) construct and TRbeta/RXRalpha with T3, the activity of LXRE containing construct was markedly increased.
CONCLUSION
We confirmed that thyroid hormone increased expression of ABCG5/8. This result suggested that thyroid hormone played an important role in decreasing serum cholesterol through bile excretion.

Keyword

Thyroid hormones; ABCG5; ABCG8; Bile; Cholesterol

MeSH Terms

Animals
Bile
Cholesterol
Hep G2 Cells
Hepatocytes
Homeostasis
Humans
Liver
Mice
Orphan Nuclear Receptors
Plasmids
Rats
Receptors, Thyroid Hormone
Response Elements
Retinoid X Receptors
RNA
RNA, Messenger
Thyroid Gland
Thyroid Hormones
Cholesterol
Orphan Nuclear Receptors
RNA
RNA, Messenger
Receptors, Thyroid Hormone
Retinoid X Receptors
Thyroid Hormones