Thyroid hormone receptor
Encyclopedia
The thyroid hormone receptor (TR) is a type of nuclear receptor
that is activated by binding thyroid hormone
.
and heart rate
. In addition, they play critical roles in the development
of organisms.
by binding to hormone response element
s (HREs) in DNA either as monomer
s, heterodimers
with retinoid X receptor
(RXR; which in turn is activated by binding to 9-cis-retinoic acid
) or as homodimers. However TR/RXR heterodimers are the most transcriptionally active
form of TR.
In the absence of hormone, TR in complex with corepressor proteins bind to HREs in a transcriptionally inactive state. Binding of thyroid hormone results in a conformational change in TR which displaces corepressor from the receptor/DNA complex and recruitment of coactivator
proteins. The DNA/TR/coactivator complex then recruits RNA polymerase
that transcribes downstream DNA into messenger RNA
and eventually protein that results in a change in cell function.
receptor designated alpha-1, beta-1 and beta-2 that are able to bind thyroid hormone.
There are two TR-α
receptor splice variants encoded by the THRA gene and two TR-β
isoform splice variants encoded by the THRB gene:
.
Nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...
that is activated by binding thyroid hormone
Thyroid hormone
The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
.
Function
Amongst the most important functions of thyroid hormone receptors are regulation of metabolismMetabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
and heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
. In addition, they play critical roles in the development
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
of organisms.
Mechanism of action
Thyroid hormone receptors regulate gene expressionRegulation of gene expression
Gene modulation redirects here. For information on therapeutic regulation of gene expression, see therapeutic gene modulation.Regulation of gene expression includes the processes that cells and viruses use to regulate the way that the information in genes is turned into gene products...
by binding to hormone response element
Hormone response element
A hormone response element is a response element for hormones, a short sequence of DNA within the promoter of a gene that is able to bind a specific hormone receptor complex and therefore regulate transcription...
s (HREs) in DNA either as monomer
Monomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...
s, heterodimers
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
with retinoid X receptor
Retinoid X receptor
The retinoid X receptor is a type of nuclear receptor that is activated by 9-cis retinoic acid. There are three retinoic X receptors : RXR-alpha, RXR-beta, and RXR-gamma, encoded by the , , genes, respectively....
(RXR; which in turn is activated by binding to 9-cis-retinoic acid
Retinoic acid
Retinoic acid is a metabolite of vitamin A that mediates the functions of vitamin A required for growth and development. Retinoic acid is required in chordate animals which includes all higher animals from fishes to humans...
) or as homodimers. However TR/RXR heterodimers are the most transcriptionally active
form of TR.
In the absence of hormone, TR in complex with corepressor proteins bind to HREs in a transcriptionally inactive state. Binding of thyroid hormone results in a conformational change in TR which displaces corepressor from the receptor/DNA complex and recruitment of coactivator
Coactivator (genetics)
A coactivator is a protein that increases gene expression by binding to an activator which contains a DNA binding domain. The coactivator is unable to bind DNA by itself....
proteins. The DNA/TR/coactivator complex then recruits RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
that transcribes downstream DNA into messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
and eventually protein that results in a change in cell function.
Isoforms
There are three forms of the thyroid hormoneThyroid hormone
The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
receptor designated alpha-1, beta-1 and beta-2 that are able to bind thyroid hormone.
There are two TR-α
Thyroid hormone receptor alpha
Thyroid hormone receptor alpha also known as nuclear receptor subfamily 1, group A, member 1 , is a nuclear receptor protein that in humans is encoded by the THRA gene.- Function :...
receptor splice variants encoded by the THRA gene and two TR-β
Thyroid hormone receptor beta
Thyroid hormone receptor beta also known as nuclear receptor subfamily 1, group A, member 2 , is a nuclear receptor protein that in humans is encoded by the THRB gene.- Function :...
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 oncogene c-erb-A, also widely expressed but unable to bind hormone)
- TR-β1 (predominately expressed in brain, liver and kidney)
- TR-β2 (expression primarily limited to the hypothalamus and pituitary)
Disease linkage
Certain mutations in the thyroid hormone receptor are associated with thyroid hormone resistanceThyroid hormone resistance
Thyroid hormone resistance describes a rare syndrome where the thyroid hormone levels are elevated but the thyroid stimulating hormone level is not suppressed, or not completely suppressed as would be expected.-Causes:...
.