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In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
Published on: October 6, 2023
Mouse sterol response element binding protein-1c gene expression is negatively regulated by thyroid hormone
Koshi Hashimoto1, Masanobu Yamada, Shunichi Matsumoto
1Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, 3-39-15 Showa-machi Maebashi, Gunma 371-8511, Japan. khashi@med.gunma-u.ac.jp
Endocrinology
|June 24, 2006
Summary
Thyroid hormone (T3) negatively regulates sterol regulatory element-binding protein (SREBP)-1c gene expression in the liver. This study identifies a novel regulatory element responsible for T3-mediated down-regulation of SREBP-1c transcription.
Area of Science:
- Molecular Biology
- Endocrinology
- Metabolism
Background:
- Sterol regulatory element-binding protein (SREBP)-1c is a crucial regulator of lipogenesis.
- The influence of thyroid hormone on SREBP-1c mRNA levels has been previously debated.
Purpose of the Study:
- To investigate the effect of thyroid hormone (T3) on mouse SREBP-1c mRNA expression.
- To elucidate the molecular mechanism underlying T3-mediated regulation of SREBP-1c.
Main Methods:
- Ribonuclease protection assays and quantitative RT-PCR to measure mRNA levels.
- Luciferase reporter assays for promoter analysis.
- Gel shift and chromatin immunoprecipitation assays to assess protein-DNA interactions.
Main Results:
- T3 was found to negatively regulate mouse SREBP-1c gene expression in the liver.
- A specific DNA sequence, Site2, within the SREBP-1c promoter was identified as critical for T3's negative effect.
- Thyroid hormone receptor-beta/retinoid X receptor-alpha heterodimers bind to Site2, mediating T3-induced gene repression in vivo.
Conclusions:
- Mouse SREBP-1c mRNA is down-regulated by T3 in the liver.
- T3 transcriptionally represses the mouse SREBP-1c gene through a novel negative thyroid hormone response element (Site2).
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