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Concept
Thyroid hormone receptor
Summary
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 is transported into the cell through a transporter. Once inside of the cell, the hormone can have genomic or non-genomic effects. The genomic signaling pathway directly influences gene transcription and translation, while the non-genomic pathway involves more rapid, cellular changes, some of which also regulate gene expression through more indirect signaling.
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. Dimerizing with different nuclear receptors leads to the regulation of different genes.
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