Thyroid hormone receptors and resistance to thyroid hormone disorders.

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Ortiga-Carvalho TM, Sidhaye AR, Wondisford FE

Thyroid hormone receptors and resistance to thyroid hormone disorders.

Nat Rev Endocrinol. 2014 Oct;10(10):582-91. doi: 10.1038/nrendo.2014.143. Epub 2014 Aug 19.

PubMed ID

25135573 [ View in PubMed

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Abstract

Thyroid hormone action is predominantly mediated by thyroid hormone receptors (THRs), which are encoded by the thyroid hormone receptor alpha (THRA) and thyroid hormone receptor beta (THRB) genes. Patients with mutations in THRB present with resistance to thyroid hormone beta (RTHbeta), which is a disorder characterized by elevated levels of thyroid hormone, normal or elevated levels of TSH and goitre. Mechanistic insights about the contributions of THRbeta to various processes, including colour vision, development of the cochlea and the cerebellum, and normal functioning of the adult liver and heart, have been obtained by either introducing human THRB mutations into mice or by deletion of the mouse Thrb gene. The introduction of the same mutations that mimic human THRbeta alterations into the mouse Thra and Thrb genes resulted in distinct phenotypes, which suggests that THRA and THRB might have non-overlapping functions in human physiology. These studies also suggested that THRA mutations might not be lethal. Seven patients with mutations in THRalpha have since been described. These patients have RTHalpha and presented with major abnormalities in growth and gastrointestinal function. The hypothalamic-pituitary-thyroid axis in these individuals is minimally affected, which suggests that the central T3 feedback loop is not impaired in patients with RTHalpha, in stark contrast to patients with RTHbeta.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Thyroid, porcine	Thyroid hormone receptor alpha	Protein	Humans	Unknown	Substrate	Details
Thyroid, porcine	Thyroid hormone receptor beta	Protein	Humans	Unknown	Substrate	Details