Thyroid hormone receptor beta: Relevance in human health and diseases

Thyroid Hormone Receptor (THR) is a member of the nuclear receptor (NR) superfamily, best defined as intracellular ligand-modulated transcription factors. Thyroid hormone (TH), by binding to THR, regulates several physiological and metabolic processes, e.g., development, metabolism, homeostasis, reproduction, etc. THR primarily heterodimerizes with RXR and binds to its response element to modulate the expression of the target genes. THR has two different isoforms differentially expressed throughout the body, i.e., THRα and THRβ, encoded by two distinct genes, THRA and THRB, respectively. The indispensable roles of THRβ in the regulation of the hypothalamus-pituitary-thyroid in addition to biochemical processes, including metabolism, hepatic and kidney-related functions, etc., illustrate that receptor dysregulations are the underlying cause of the onset of several diseases, including diabetes, cardiac ailments, metabolic-related disorders, endocrine-related cancers, reproductive issues, etc. This also makes it a potential target for pharmacological interventions. In this context, the present review focuses mainly on the intrinsic mechanism of THRβ functioning and its contribution to disease progression. In addition, several genetic/polymorphic variations in the THRB gene that are primary driving factors in eliciting rare genetic disorder, i.e., resistance to thyroid hormone (RTH), have also been addressed in detail. We have also highlighted the implications of THR targetability by addressing the impact of TH analogs/modulators and thyroid hormone-disrupting chemicals in disease occurrence and its management.