[Thyroid hormone receptors and its disorders].

Resistance to thyroid hormone (RTH) is a genetic disease caused by mutations of thyroid hormone receptor beta gene. RTH is manifested by inappropriately elevated levels of serum thyrotropin in the presence of elevated circulating thyroid hormones. Most of the patients with RTH do not manifest remarkable clinical features, but may represent partial hypothyroidism. Sometimes even tachycardia, sweating, body weight loss or attention-deficit hyperactivity disorder are found. TR beta mutants, which have reduced T3-binding activities and aberrant interactions with transcriptional cofactors, act in a dominant negative fashion against wild type TRs. Although no human disease has been found to be caused by TR alpha gene mutations, TR alpha knockout mice suggest that TR alpha plays a major role in the regulation of heart rate and basal metabolism and TR alpha gene-deficiency does not express the RTH phenotype.