Thyroid Hormone Receptor Assays
Background of Thyroid Hormone Receptors (THRs)
Thyroid hormones (THs) are critical for many processes in the body, and abnormal thyroid hormone signaling has been implicated in a variety of human diseases. Most of the actions of THs are mediated by THRs. THRs are considered to be a class of transcription factors with ligand-regulated activity. By regulating the transcription of target genes in response to ligands, THRs play central physiological roles in many aspects of growth, development, homeostasis, and metabolism.
Distribution and Function of THRs
THRs are widely distributed in bone, gastrointestinal tract, cardiac and skeletal muscle, and the central nervous system with the highest expression; TRα2 and TRα3 are mainly found in the brain, kidney, testis, brown adipose tissue, and skeletal muscle. In addition, THRs also have an impact on stem cell function. Notably, it has been reported that THRs are associated with tumorigenesis.
Fig.1. Overview of thyroid hormone action. (Ortiga-Carvalho, 2014)
Mechanisms of THRs
There are two major THR isoforms THRα and THRβ that have been shown to mediate the biological activity of thyroid hormones. The following table summarizes the relevant information.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| THRα | THRA |
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| THRβ | THRB |
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Published Data
| Paper Title | The prognostic impact of retinoid X receptor and thyroid hormone receptor alpha in unifocal vs. multifocal/multicentric breast cancer |
| Journal | International Journal of Molecular Sciences |
| Published | 2021 |
| Abstract | The primary objective of this study was to evaluate the prognostic value of steroid hormone receptor expression, calculating THRs and retinoic acid X receptors (RXR) against two different breast cancer (BC) entities. Overall survival and disease-free survival were believed to be key prognostic indicators and were analyzed by univariate and multivariate analyses. The expression of THRs, including the two isoforms THRα1 and THRα2, was analyzed by immunohistochemistry and showed a significant correlation for both BC entities in survival analysis. |
| Result |
In this study, THRα1 and THRα2 were strongly associated with the prognosis of two distinct BC entities, but there were large differences. Unifocal BC patients showed worse disease-free survival (DFS) when THRα1 was expressed. In contrast, a significant correlation between THRα1 expression was not detected in the survival analysis of multifocal/multicentric BC. On the other hand, in multifocal/multicentric BC, there was a positive association between high THRα2 expression and enhanced DFS. It is worth noting that a statistically significant association between monofocal BC and THRα2 expression has not yet been detected.
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Fig.2. Immunohistochemical staining of RXR and THRα2. (Zehni, 2021)
References
- Ortiga-Carvalho, T. M.; et al. Thyroid hormone receptors and resistance to thyroid hormone disorders. Nature Reviews Endocrinology. 2014; 10(10): 582-591.
- Zehni, A.Z.; et al. The prognostic impact of retinoid X receptor and thyroid hormone receptor alpha in unifocal vs. multifocal/multicentric breast cancer. International Journal of Molecular Sciences. 2021; 22(2): 957.
