TR (Thyroid Hormone Receptors)
RXR and its Brothers

Author: Gianpiero Pescarmona
Date: 30/04/2012

Description

The thyroid hormone receptor is a type of nuclear receptor that is activated by binding thyroid hormone.
There are three forms of the thyroid hormone receptor designated alpha-1, beta-1 and beta-2 that are able to bind thyroid hormone. There are two TR-alpha receptor splice variants encoded by the THRA gene and two TR-beta isoform splice variants encoded by the THRB gene:

  • TR-α1 (widely expressed and especially high expression in cardiac and skeletal muscles)
  • TR-α2 (homologous with viral oncogen c-erb-A, also widely expressed but unable to bind hormone)
  • TR-β1 (predominantely expressed in brain, liver and kidney)
  • TR-β2 (expression primarily limited to the hypothalamus and pituitary)

The TR-beta-deficient mice showed an elevated heart rate, which, however, was unresponsive to thyroid hormone treatment regardless of hormonal serum levels

1999

The liver, ear and retina have also been identified as TRβ target tissues whilst the heart, like bone, is a TRα1 target organ (ref 2006)
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Thyroid Hormone Resistance

MULTIPLE ETIOLOGIES FOR REDUCED SENSITIVITY TO THYROID HORMONE 2006

Certain mutations in the thyroid hormone receptor are associated with thyroid hormone resistance.

Regulation of TR expression

Nuclear localization of protein kinase C-alpha induces thyroid hormone receptor-alpha1 expression in the cardiomyocyte. 2006

Action mechanism

Thyroid hormones can have either genomic or non genomic effects

Genomic

As the target genes of thyroid hormone are located on both nuclear and mitochondrial DNA their expression requires a tight coordination

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Thyroid and Estrogens
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Mitochondrial proteins

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