Thyroid Hormone Receptor Related Drug Discovery Products

Thyroid hormone receptors (THRs), a nuclear receptor assemblage, partake in critical capacities in mediating the manifold repercussions of thyroid hormones on an array of physiological phenomena, encompassing cellular metabolism, ontogenesis, and homeostatic equilibrium. As quintessential orchestrators of gene expression concomitant with thyroid hormone signaling, THRs have garnered substantial fascination as prospective therapeutic objectives for a multitude of maladies.

Creative Biolabs offers thyroid hormone receptor drug discovery products to help research groups accelerate drug discovery and development:

• Thyroid Hormone Receptor Assays
• Membrane Protein Tools

Overview of Thyroid Hormone Receptor

Thyroid hormone receptors (THRs) are nuclear receptors that regulate gene expression in response to thyroid hormones, such as triiodothyronine (T3) and thyroxine (T4). The THR family comprises two major subtypes, THRα and THRβ, each encoded by distinct genes (THRA and THRB, respectively) and exhibiting tissue-specific expression patterns. Both subtypes have multiple isoforms resulting from alternative splicing or the use of alternative promoters, which contribute to the complexity and functional diversity of the THR signaling pathways.

Fig.1 The THRα and THRβ isoforms have considerable homology. (Ortiga-Carvalho, 2014)

THRα: The THRA gene encodes two main isoforms, THRα1 and THRα2. These isoforms share a common DNA-binding domain, but differ in their ligand-binding domains, which results in distinct ligand-binding properties and transcriptional activities. THRα1 is the primary isoform that binds T3 with high affinity, mediating the classical actions of thyroid hormones in various tissues, including the brain, heart, and skeletal muscle. In contrast, THRα2 lacks a functional ligand-binding domain and acts as a dominant-negative regulator of THRα1, modulating its transcriptional activity in a ligand-independent manner. Additional isoforms, such as THRα3 and THRαΔE9, have been identified, but their functional roles are less well understood.

THRβ: The THRB gene gives rise to three major isoforms, THRβ1, THRβ2, and THRβ3, which differ in their N-terminal regions due to alternative splicing. All three isoforms possess functional DNA-binding and ligand-binding domains, enabling them to bind T3 and regulate target gene expression. THRβ1 is widely expressed in various tissues, including the liver, kidney, and heart, where it plays a key role in regulating metabolic processes and maintaining cardiovascular homeostasis. THRβ2 has a more restricted expression pattern, primarily in the hypothalamus, pituitary, and retina, and is involved in the regulation of the hypothalamic-pituitary-thyroid axis and visual function. THRβ3 is predominantly expressed in the cochlea and testis, but its specific functional role remains to be elucidated.

Thyroid Hormone Receptor Drug Discovery

The critical roles of THRs in numerous physiological processes have fueled efforts to explore their potential as therapeutic targets for various diseases. Key areas of focus in drug discovery involving THRs include:

Fig.2 Overview of tissues and homeostatic functions affected in THRB/THRA mutation. (Ortiga-Carvalho, 2014)

Reference

1. Ortiga-Carvalho, T.; et al. Thyroid hormone receptors and resistance to thyroid hormone disorders. Nature Reviews Endocrinology. 2014, 10: 582-591.