Thyroid hormone receptor

Nuclear protein

The thyroid hormone receptor (TR) is a type of nuclear receptor that is activated by binding thyroid hormone. TRs act as transcription factors, ultimately affecting the regulation of gene transcription and translation. These receptors also have non genomic effects that lead to second messenger activation, and corresponding cellular response.

There are four domains that are present in all TRs. Two of these, the DNA binding (DBD) and hinge domains, are involved in the ability of the receptor to bind hormone response elements (HREs). TRs also have a ligand binding domain (LBD) that allows them to bind to thyroid hormone with high affinity. The fourth domain is a transactivation domain which allows the receptor to bind other transcription factors.

Thyroid hormone receptors play critical roles in the regulation of metabolism, heart rate, and development of organisms. These receptors are typically associated with retinoic acid receptors (RXR), forming heterodimers. In its inactivated form, the TR inhibits gene transcription by binding corepressors. This adds an additional level of regulation to an already tightly regulated process. When activated, these receptors become associated with other activators and initiate gene transcription. TRs are also involved in cell viability, and are believed to have other non genomic affects that are currently being investigated.

Thyroid hormone receptors regulate gene expression by binding to hormone response elements (HREs) in DNA either as monomers, heterodimers with other nuclear receptors, or homodimers. TR/RXR heterodimers are the most transcriptionally active form of TR.

Retinoic acid receptors are located in the nucleus and commonly form complexes with steroid hormone receptors in order to regulate the production of essential gene products. Initially most scientists presumed that non genomic effects were mediated by non nuclear receptors, but now there is growing evidence for non genomic effects mediated in the cytoplasm by the traditional nuclear receptors. For example, TR α1 (a specific isoform of TR) has been linked to cell viability, which allowed scientists to obtain direct genetic evidence for the involvement of TR β signaling through the PI3 kinase in brain development two of the primary physiological effects of thyroid hormone action.

There are two main classes of the thyroid hormone receptor, alpha and beta. The clinical diagnosis of thyroid hormone resistance syndrome (THRS) depends on the location of the resistance, which can be localized to the pituitary gland, peripheral tissues, or both. Patients who present with resistance in both tissue types are diagnosed with global resistance to thyroid hormone. Mutations to both TR genes have been observed clinically, however, THRB gene mutations are much more common.

TR β resistance is an autosomal dominant disease. Beta blockers are competitive inhibitors of adrenaline, the post ganglionic neurotransmitter released by cells of the sympathetic nervous system. By blocking the ability of receptors to bind adrenaline, beta blockers have been observed to alleviate symptoms of anxiety, increased blood pressure, and irregular heartbeat, amongst others. Anti anxiety medications can also be prescribed to individuals with this conditions to treat symptoms of anxiety.