Thyroid Hormone Regulates the mRNA Expression of Small Heterodimer Partner through Liver Receptor Homolog-1.
BACKGROUND
Expression of hepatic cholesterol 7α-hydroxylase (CYP7A1) is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP). In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1).


METHODS
We injected thyroid hormone (triiodothyronine, T3) to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR). Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA) were also performed using human hepatoma cell line.


RESULTS
Initial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor β/retinoid X receptor α/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding.


CONCLUSIONS
We found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
Hwa Young
HY
Ahn
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Hwan Hee
HH
Kim
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Ye An
YA
Kim
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Min
M
Kim
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Jung Hun
JH
Ohn
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Sung Soo
SS
Chung
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Yoon Kwang
YK
Lee
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Do Joon
DJ
Park
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Kyong Soo
KS
Park
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. moore@bcm.tmc.edu.
David D
DD
Moore
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. yjparkmd@snu.ac.kr.
Young Joo
YJ
Park
Bile acids and salts; Cholesterol; Liver receptor homolog-1; Small heterodimer partner; Thyroid hormones