갑상선호르몬이 ATP-binding Cassette Sterol Transporter ABCG5의 발현에 미치는 영향
Effect of Thyroid Hormone to the Expression of ATP-binding Cassette Transporter ABCG5
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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)β/human retinoid X receptor (hRXR)α or human liver X receptor (hLXR)α 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. LXRα mRNA was not increased by T3. However, when we cotransfected liver X receptor response element (LXRE) construct and TRβ/RXRα 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.
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)β/human retinoid X receptor (hRXR)α or human liver X receptor (hLXR)α 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. LXRα mRNA was not increased by T3. However, when we cotransfected liver X receptor response element (LXRE) construct and TRβ/RXRα 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.
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