Thyrotropin receptor

Last updated
TSHR
Protein TSHR PDB 1XUM.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TSHR , CHNG1, LGR3, hTSHR-I, thyroid stimulating hormone receptor, Thyrotropin receptor
External IDs OMIM: 603372 MGI: 98849 HomoloGene: 315 GeneCards: TSHR
Gene location (Human)
Ideogram human chromosome 14.svg
Chr. Chromosome 14 (human) [1]
Human chromosome 14 ideogram.svg
HSR 1996 II 3.5e.svg
Red rectangle 2x18.png
Band 14q31.1Start80,954,989 bp [1]
End81,146,302 bp [1]
RNA expression pattern
PBB GE TSHR 210055 at fs.png

PBB GE TSHR 215442 s at fs.png

PBB GE TSHR 215443 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000369
NM_001018036
NM_001142626

NM_001113404
NM_011648

RefSeq (protein)

NP_000360
NP_001018046
NP_001136098

NP_001106875
NP_035778

Location (UCSC) Chr 14: 80.95 – 81.15 Mb Chr 12: 91.38 – 91.55 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The thyrotropin receptor (or TSH receptor) is a receptor (and associated protein) that responds to thyroid-stimulating hormone (also known as "thyrotropin") and stimulates the production of thyroxine (T4) and triiodothyronine (T3). The TSH receptor is a member of the G protein-coupled receptor superfamily of integral membrane proteins [5] and is coupled to the Gs protein. [6]

Contents

It is primarily found on the surface of the thyroid epithelial cells, but also found on adipose tissue and fibroblasts. The latter explains the reason of the myxedema finding during Graves disease.

Function

Upon binding circulating TSH, a G-protein signal cascade activates adenylyl cyclase and intracellular levels of cAMP rise. cAMP activates all functional aspects of the thyroid cell, including iodine pumping; thyroglobulin synthesis, iodination, endocytosis, and proteolysis; thyroid peroxidase activity; and hormone release.

See also

Related Research Articles

Hyperthyroidism thyroid gland disease that involves an over Production of thyroid hormone.

Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerance, diarrhea, enlargement of the thyroid, hand tremor, and weight loss. Symptoms are typically less severe in the elderly and during pregnancy. An uncommon complication is thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature and often results in death. The opposite is hypothyroidism, when the thyroid gland does not make enough thyroid hormone.

Graves disease Autoimmune endocrine disease

Graves' disease, also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyroid. Signs and symptoms of hyperthyroidism may include irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhea and unintentional weight loss. Other symptoms may include thickening of the skin on the shins, known as pretibial myxedema, and eye bulging, a condition caused by Graves' ophthalmopathy. About 25 to 80% of people with the condition develop eye problems.

Thyrotropin-releasing hormone hormone

Thyrotropin-releasing hormone (TRH), is a hypophysiotropic hormone, produced by neurons in the hypothalamus, that stimulates the release of thyroid-stimulating hormone (TSH) and prolactin from the anterior pituitary.

Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone produced by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid.

Thyroxine-binding globulin mammalian protein found in Homo sapiens

Thyroxine-binding globulin (TBG) is a globulin protein that in humans is encoded by the SERPINA7 gene. TBG binds thyroid hormones in circulation. It is one of three transport proteins (along with transthyretin and serum albumin) responsible for carrying the thyroid hormones thyroxine (T4) and triiodothyronine (T3) in the bloodstream. Of these three proteins, TBG has the highest affinity for T4 and T3 but is present in the lowest concentration. Despite its low concentration, TBG carries the majority of T4 in the blood plasma. Due to the very low concentration of T4 and T3 in the blood, TBG is rarely more than 25% saturated with its ligand. Unlike transthyretin and albumin, TBG has a single binding site for T4/T3. TBG is synthesized primarily in the liver as a 54-kDa protein. In terms of genomics, TBG is a serpin; however, it has no inhibitory function like many other members of this class of proteins.

Thyroid disease type of endocrine disease

Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning that it is an endocrine organ. These hormones normally act in the body to regulate energy use, infant development, and childhood development.

Toxic multinodular goiter is an active multinodular goiter associated with hyperthyroidism.

Thyroid function tests (TFTs) is a collective term for blood tests used to check the function of the thyroid.

Follicle-stimulating hormone receptor protein-coding gene in the species Homo sapiens

The follicle-stimulating hormone receptor or FSH receptor (FSHR) is a transmembrane receptor that interacts with the follicle-stimulating hormone (FSH) and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormonal functioning of FSH. FSHRs are found in the ovary, testis, and uterus.

Luteinizing hormone/choriogonadotropin receptor protein-coding gene in the species Homo sapiens

The luteinizing hormone/choriogonadotropin receptor (LHCGR), also lutropin/choriogonadotropin receptor (LCGR) or luteinizing hormone receptor (LHR) is a transmembrane receptor found predominantly in the ovary and testis, but also many extragonadal organs such as the uterus and breasts. The receptor interacts with both luteinizing hormone (LH) and chorionic gonadotropins and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormonal functioning during reproduction.

Thyrotropin-releasing hormone receptor protein-coding gene in the species Homo sapiens

Thyrotropin-releasing hormone receptor (TRHR) is a G protein-coupled receptor which binds thyrotropin-releasing hormone.

Hypothalamic–pituitary–thyroid axis part of the neuroendocrine system responsible for the regulation of metabolism.

The hypothalamic–pituitary–thyroid axis is part of the neuroendocrine system responsible for the regulation of metabolism and also responds to stress.

Euthyroid sick syndrome (ESS) is a state of adaptation or dysregulation of thyrotropic feedback control wherein the levels of T3 and/or T4 are abnormal, but the thyroid gland does not appear to be dysfunctional. This condition may result from allostatic responses of hypothalamsus-pituitary-thyroid feedback control, dyshomeostatic disorders, drug interferences and impaired assay characteristics in critical illness.

Sodium/iodide cotransporter mammalian protein found in Homo sapiens

The sodium/iodide cotransporter, also known as the sodium/iodide symporter (NIS), is a protein that in humans is encoded by the SLC5A5 gene. It is a transmembrane glycoprotein with a molecular weight of 87 kDa and 13 transmembrane domains, which transports two sodium cations (Na+) for each iodide anion (I) into the cell. NIS mediated uptake of iodide into follicular cells of the thyroid gland is the first step in the synthesis of thyroid hormone.

Thyroid hormone receptor beta protein-coding gene in the species Homo sapiens

Thyroid hormone receptor beta (TR-beta) also known as nuclear receptor subfamily 1, group A, member 2 (NR1A2), is a nuclear receptor protein that in humans is encoded by the THRB gene.

Thyroid hormones hormones produced by the thyroid gland

Thyroid hormones are two hormones produced and released by the thyroid gland, namely triiodothyronine (T3) and thyroxine (T4). They are tyrosine-based hormones that are primarily responsible for regulation of metabolism. T3 and T4 are partially composed of iodine. A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as simple goitre. The major form of thyroid hormone in the blood is thyroxine (T4), which has a longer half-life than T3. In humans, the ratio of T4 to T3 released into the blood is approximately 14:1. T4 is converted to the active T3 (three to four times more potent than T4) within cells by deiodinases (5′-iodinase). These are further processed by decarboxylation and deiodination to produce iodothyronamine (T1a) and thyronamine (T0a). All three isoforms of the deiodinases are selenium-containing enzymes, thus dietary selenium is essential for T3 production.

TSHB protein-coding gene in the species Homo sapiens

Thyroid stimulating hormone, beta also known as TSHB is a protein which in humans is encoded by the TSHB gene.

Thyroid disease in pregnancy can affect the health of the mother as well as the child before and after delivery. Thyroid disorders are prevalent in women of child-bearing age and for this reason commonly present as an intercurrent disease in pregnancy and the puerperium. Uncorrected thyroid dysfunction in pregnancy has adverse effects on fetal and maternal well-being. The deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neurointellectual development in the early life of the child. Due to an increase in thyroxine binding globulin, an increase in placental type 3 deioidinase and the placental transfer of maternal thyroxine to the fetus, the demand for thyroid hormones is increased during pregnancy. The necessary increase in thyroid hormone production is facilitated by high human chorionic gonadotropin (hCG) concentrations, which bind the TSH receptor and stimulate the maternal thyroid to increase maternal thyroid hormone concentrations by roughly 50%. If the necessary increase in thyroid function cannot be met, this may cause a previously unnoticed (mild) thyroid disorder to worsen and become evident as gestational thyroid disease. Currently, there is not enough evidence to suggest that screening for thyroid dysfunction is beneficial, especially since treatment thyroid hormone supplementation may come with a risk of overtreatment. After women give birth, about 5% develop postpartum thyroiditis which can occur up to nine months afterwards.This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid.

Antithyroid autoantibodies (or simply antithyroid antibodies) are autoantibodies targeted against one or more components on the thyroid. The most clinically relevant anti-thyroid autoantibodies are anti-thyroid peroxidase antibodies (anti-TPO antibodies, TPOAb), thyrotropin receptor antibodies (TRAb) and thyroglobulin antibodies (TgAb). TRAb's are subdivided into activating, blocking and neutral antibodies, depending on their effect on the TSH receptor. Anti-sodium/Iodide (Anti–Na+/I) symporter antibodies are a more recent discovery and their clinical relevance is still unknown. Graves' disease and Hashimoto's thyroiditis are commonly associated with the presence of anti-thyroid autoantibodies. Although there is overlap, anti-TPO antibodies are most commonly associated with Hashimoto's thyroiditis and activating TRAb's are most commonly associated with Graves' disease. Thyroid microsomal antibodies were a group of anti-thyroid antibodies, they were renamed after the identification of their target antigen (TPO).

The sum activity of peripheral deiodinases is the maximum amount of triiodothyronine produced per time-unit under conditions of substrate saturation. It is assumed to reflect the activity of deiodinases outside the central nervous system and other isolated compartments. GD is therefore expected to reflect predominantly the activity of type I deiodinase.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000165409 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020963 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Farid NR, Szkudlinski MW (Sep 2004). "Minireview: structural and functional evolution of the thyrotropin receptor". Endocrinology. 145 (9): 4048–57. doi: 10.1210/en.2004-0437 . PMID   15231707.
  6. Calebiro D, Nikolaev VO, Lohse MJ (Jul 2010). "Imaging of persistent cAMP signaling by internalized G protein-coupled receptors". Journal of Molecular Endocrinology. 45 (1): 1–8. doi: 10.1677/JME-10-0014 . PMID   20378719.

Further reading