TR alpha 1
Thyroid hormone receptor alpha-1, a major isoform produced from the THRA gene, is a ligand-dependent transcription factor of the nuclear receptor superfamily. In the absence of hormone it binds thyroid hormone response elements together with corepressors such as NCoR, and T3 binding triggers coactivator recruitment and target-gene activation. TR alpha-1 predominates in heart, brain, brown adipose tissue, skeletal muscle and bone, governing heart rate, thermogenesis and skeletal development. Unlike TR beta-selective forms of resistance, heterozygous THRA mutations cause resistance to thyroid hormone alpha syndrome, characterized by hypothyroid-like features in tissues dominated by TR alpha-1 with near-normal serum thyroid tests. Recombinant TR alpha-1 ligand-binding domain is widely used to screen thyromimetics, including TR beta-selective agents developed for metabolic liver disease.
