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Updated: May 7, 2026
04:14
In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
Published on: October 6, 2023
Receptors of thyroid hormones.
Ana Aranda1, Elvira Alonso-Merino, Alberto Zambrano
1Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Arturo Duperier 4, 28029 Madrid, Spain. aaranda@iib.uam.es
Pediatric Endocrinology Reviews : PER
|October 2, 2013
Summary
Thyroid hormone receptors (TRs) control gene expression. TRbeta-selective drugs may treat metabolic disorders, while TRalpha mutations cause hypothyroidism symptoms despite normal thyroid hormone levels.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Thyroid hormones exert physiological effects via nuclear thyroid hormone receptors (TRs), encoded by TRalpha and TRbeta genes.
- TRs function as hormone-dependent transcription factors, modulating gene expression through DNA binding and coregulator recruitment.
- TRbeta-selective thyromimetics show potential for treating hyperlipidemia and obesity.
Purpose of the Study:
- To explore the therapeutic potential of TRbeta-selective thyromimetics.
- To investigate the clinical manifestations of TRbeta gene mutations causing resistance to thyroid hormones (RTH).
- To describe recent findings in patients with heterozygous TRalpha mutations.
Main Methods:
- Review of existing literature on thyroid hormone receptor function and related pathologies.
- Analysis of clinical data from patients with TRbeta mutations (RTH) and TRalpha mutations.
- Characterization of novel thyromimetics targeting TRbeta.
Main Results:
- TRbeta gene mutations lead to RTH, characterized by elevated TSH and reduced tissue sensitivity to thyroid hormones.
- Novel thyromimetics preferentially binding TRbeta are under development for metabolic diseases.
- Heterozygous TRalpha mutations result in hypothyroidism symptoms in specific tissues (e.g., heart, intestine) with near-normal TSH and thyroid hormone levels.
Conclusions:
- TRbeta-selective agents offer a promising avenue for treating hyperlipidemia and obesity.
- Understanding TR mutations is crucial for diagnosing and managing thyroid hormone-related disorders.
- TRalpha and TRbeta play distinct, critical roles in thyroid hormone action and overall physiology.
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About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
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