Thyroid hormone receptors in health and disease (original) (raw)

2012, Minerva endocrinologica

Abstract

Thyroid hormones (TH) play a key role in energy homeostasis throughout life. Thyroid hormone production and secretion by the thyroid gland is regulated via the hypothalamus-pituitary-thyroid (HPT)-axis. Thyroid hormone has to be transported into the cell, where it can bind to the thyroid hormone receptor (TR) in the nucleus to exert its effect on cellular gene-transcription. Mutations in both the THRA and THRB gene have been described, each inducing a characteristic phenotype clearly showing the selective effect of an excess or shortage of thyroid hormone in specific TRα and TRβ regulated organs. Profound changes in thyroid hormone metabolism occur during a variety of non-thyroidal illnesses, each associated with reduced TR expression in a tissue-specific manner. However, thyroid hormone action at the tissue level during illness is not a simple reflection of the extent of TR expression as illness has additional differential effects on local thyroid hormone availability in various or...

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FAQs

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What are the roles of TRα and TRβ in thyroid hormone action?add

TRα is primarily involved in metabolic effects, while TRβ regulates feedback in the HPT-axis, influencing serum hormone levels significantly.

How do mutations in thyroid hormone receptors impact clinical syndromes?add

Heterozygous mutations in the TRβ gene are the most common cause of resistance to thyroid hormone syndrome, characterized by elevated thyroid hormones without TSH suppression.

What does the study reveal about deiodinase regulation during illness?add

TRs influence the expression of deiodinases like D1 and D2, where D1 activity decreases during illness, affecting T3 metabolism across tissues.

Why do thyroid hormones exhibit non-genomic actions?add

Thyroid hormones interact with integrin receptors and activate signaling pathways like PI3K, allowing rapid cellular responses independent of gene transcription.

How do thyroid hormone transporters affect cellular hormone uptake?add

Transporters like MCT-8 and OATP-1C1 facilitate T4 and T3 uptake, essential for effective thyroid hormone signaling in target tissues.