Endocrinol Metab.  2015 Dec;30(4):584-592. 10.3803/EnM.2015.30.4.584.

Thyroid Hormone Regulates the mRNA Expression of Small Heterodimer Partner through Liver Receptor Homolog-1

Affiliations
  • 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. yjparkmd@snu.ac.kr
  • 2Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
  • 3Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. moore@bcm.tmc.edu

Abstract

BACKGROUND
Expression of hepatic cholesterol 7alpha-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 beta/retinoid X receptor alpha/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding.
CONCLUSION
We found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.

Keyword

Small heterodimer partner; Thyroid hormones; Cholesterol; Liver receptor homolog-1; Bile acids and salts
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