ArticleThe Journal of endocrinology2010
Regulation of thyroid hormone activation via the liver X-receptor/retinoid X-receptor pathway.
Article in The Journal of endocrinology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
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- Interplay between Fatty Acid Binding Protein 4, Fetuin-A, Retinol Binding Protein 4 and Thyroid Function in Metabolic Dysregulation.Metabolites · 2022Review
- Deiodinases and the Metabolic Code for Thyroid Hormone Action.Endocrinology · 2021Review
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- Paradigms of Dynamic Control of Thyroid Hormone Signaling.Endocrine reviews · 2019Review
- The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemia.Cell reports · 2018Article
- Metabolic Effects of the Intracellular Regulation of Thyroid Hormone: Old Players, New Concepts.Frontiers in endocrinology · 2018Review
- A-FABP mediates adaptive thermogenesis by promoting intracellular activation of thyroid hormones in brown adipocytes.Nature communications · 2017Article
- Review
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- Perinatal deiodinase 2 expression in hepatocytes defines epigenetic susceptibility to liver steatosis and obesity.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Liver X receptor regulation of thyrotropin-releasing hormone transcription in mouse hypothalamus is dependent on thyroid status.PloS one · 2014Article
- Cracking the code for thyroid hormone signaling.Transactions of the American Clinical and Climatological Association · 2013Article
- Minireview: cracking the metabolic code for thyroid hormone signaling.Endocrinology · 2011Review
- Both liver-X receptor (LXR) isoforms control energy expenditure by regulating brown adipose tissue activity.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Article
- A comprehensive transcriptome analysis of skeletal muscles in two Polish pig breeds differing in fat and meat quality traits.Genetics and molecular biologyArticle
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Thyroid hormone receptor (TR) and liver X-receptor (LXR) are the master regulators of lipid metabolism. Remarkably, a mouse with a targeted deletion of both LXR alpha and LXR beta is resistant to western diet-induced obesity, and exhibits ectopic liver expression of the thyroid hormone activating type 2 deiodinase (D2). We hypothesized that LXR/retinoid X-receptor (RXR) signaling inhibits hepatic D2 expression, and studied this using a luciferase reporter containing the human DIO2 (hDIO2) promoter in HepG2 cells. Given that, in contrast to mammals, the chicken liver normally expresses D2, the chicken DIO2 (cDIO2) promoter was also studied. 22(R)-OH-cholesterol negatively regulated hDIO2 in a dose-dependent manner (100 microM, approximately twofold), while it failed to affect the cDIO2 promoter. Truncations in the hDIO2 promoter identified the region -901 to -584 bp as critical for negative regulation. We also investigated if 9-cis retinoic acid (9-cis RA), the ligand for the heterodimeric partner of TR and LXR, RXR, could regulate the hDIO2 promoter. Notably, 9-cis RA repressed the hDIO2 luciferase reporter (1 microM, approximately fourfold) in a dose-dependent manner, while coexpression of an inactive mutant RXR abolished this effect. However, it is unlikely that RXR homodimers mediate the repression of hDIO2 since mutagenesis of a DR-1 at -506 bp did not interfere with 9-cis RA-mediated repression. Our data indicate that hDIO2 transcription is negatively regulated by both 22(R)-OH-cholesterol and 9-cis RA, which is consistent with LXR/RXR involvement. In vivo, the inhibition of D2-mediated tri-iodothyronine (T(3)) production by cholesterol/9-cis RA could function as a feedback loop, given that T(3) decreases hepatic cholesterol levels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.