THR - thyroid hormone receptor | Elisa - Clia - Antibody - Protein

Background

Thyroid hormone receptors (THRs) are nuclear receptors that mediate the effects of thyroid hormones, primarily triiodothyronine (T3) and thyroxine (T4). These hormones are critical for the regulation of metabolism, development, and differentiation in nearly all tissues of vertebrates. THRs act as transcription factors that bind to specific DNA sequences in the promoters of target genes, modulating their expression in response to thyroid hormone levels. The regulation by thyroid hormones is crucial for processes such as energy expenditure, thermogenesis, and the development of the central nervous system.

Protein Structure

THRs are composed of several functional domains:

• N-terminal Domain (NTD): Involved in modulating transcriptional activity and contains activation function-1 (AF-1), which can interact with coactivators.
• DNA-binding Domain (DBD): Contains two zinc finger motifs essential for binding to thyroid hormone response elements (TREs) on DNA.
• Hinge Region: Provides flexibility and connects the DBD to the ligand-binding domain (LBD).
• Ligand-binding Domain (LBD): Responsible for binding thyroid hormones. This domain also includes activation function-2 (AF-2), which mediates interactions with coactivators or corepressors depending on the presence or absence of the hormone.

Classification and Subtypes

THRs are encoded by two main genes, resulting in different isoforms:

• TRα (Thyroid Hormone Receptor Alpha): Includes TRα1 and TRα2 isoforms. TRα1 is widely expressed and functional, whereas TRα2 does not bind thyroid hormones and acts as a dominant-negative inhibitor.
• TRβ (Thyroid Hormone Receptor Beta): Includes TRβ1, TRβ2, and TRβ3 isoforms. TRβ1 is ubiquitously expressed, TRβ2 is predominantly found in the pituitary and hypothalamus, and TRβ3 is expressed in the liver and kidneys.

Function and Biological Significance

THRs regulate various physiological processes:

• Metabolism: Thyroid hormones regulate basal metabolic rate and influence carbohydrate, lipid, and protein metabolism.
• Development: Essential for the proper development of the central nervous system, skeletal system, and maturation of various organs.
• Thermogenesis: Regulate heat production and energy expenditure by modulating the expression of uncoupling proteins.
• Cardiovascular System: Influence heart rate, cardiac output, and vascular resistance.
• Growth and Differentiation: Critical for normal growth and differentiation of tissues, particularly during fetal and neonatal development.

Clinical Issues

Alterations in THR function can lead to various clinical conditions:

• Hypothyroidism: Reduced thyroid hormone levels result in decreased metabolic rate, weight gain, fatigue, and developmental delays.
• Hyperthyroidism: Excessive thyroid hormone levels cause increased metabolic rate, weight loss, heat intolerance, and nervousness.
• Thyroid Hormone Resistance Syndromes: Mutations in THR genes can lead to resistance to thyroid hormone, presenting with variable symptoms of hypo- and hyperthyroidism.

Summary

Thyroid hormone receptors (THRs) are pivotal nuclear receptors that mediate the effects of thyroid hormones, essential for numerous physiological functions. Comprising TRα and TRβ isoforms, they regulate gene expression in response to T3 and T4. THRs are involved in metabolic regulation, development, thermogenesis, and cardiovascular function. Dysregulation or mutations in THR genes can result in significant clinical disorders, including hypothyroidism, hyperthyroidism, and thyroid hormone resistance syndromes. Understanding the structure and function of THRs is crucial for diagnosing and treating thyroid-related diseases.