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, thyrotropin (TSH) receptor
External IDs OMIM: 603372 MGI: 98849 HomoloGene: 315 GeneCards: TSHR
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. In addition, it has also been found to be expressed in the anterior pituitary gland, hypothalamus and kidneys. Its presence in the anterior pituitary gland may be involved in mediating the paracrine signaling feedback inhibition of thyrotropin along the hypothalamus-pituitary-thyroid axis. [7]

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. TSHR is involved in regulating seasonal reproduction in vertebrates. [8]

See also

Related Research Articles

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.

Thyroid disease Medical condition

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.

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

Follicle-stimulating hormone receptor

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

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

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

Hypothalamic–pituitary–thyroid axis

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

Sodium/iodide cotransporter

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.

Calcium-sensing receptor

The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ions. It is primarily expressed in the parathyroid gland, the renal tubules of the kidney and the brain. In the parathyroid gland, it controls calcium homeostasis by regulating the release of parathyroid hormone (PTH). In the kidney it has an inhibitory effect on the reabsorption of calcium, potassium, sodium, and water depending on which segment of the tubule is being activated.

Testicular receptor 2

The testicular receptor 2 (TR2) also known as NR2C1 is protein that in humans is encoded by the NR2C1 gene. TR2 is a member of the nuclear receptor family of transcription factors.

Thyroid hormone receptor beta

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.

Endothelin A receptor

Endothelin receptor type A, also known as ETA, is a human G protein-coupled receptor.

Somatostatin receptor 1

Somatostatin receptor type 1 is a protein that in humans is encoded by the SSTR1 gene.

Glycoprotein hormones, alpha polypeptide

Glycoprotein hormones, alpha polypeptide is a protein that in humans is encoded by the CGA gene.

IGSF1

Immunoglobulin superfamily, member 1 is a plasma membrane glycoprotein encoded by the IGSF1 gene, which maps to the X chromosome in humans and other mammalian species.

Thyroid hormones

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.

TSHB

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 a pre-existing disease in pregnancy, or after childbirth. 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).

Pulsatile secretion is a biochemical phenomenon observed in a wide variety of cell and tissue types, in which chemical products are secreted in a regular temporal pattern. The most common cellular products observed to be released in this manner are intercellular signaling molecules such as hormones or neurotransmitters. Examples of hormones that are secreted pulsatilely include insulin, thyrotropin, TRH, gonadotropin-releasing hormone (GnRH) and growth hormone (GH). In the nervous system, pulsatility is observed in oscillatory activity from central pattern generators. In the heart, pacemakers are able to work and secrete in a pulsatile manner. A pulsatile secretion pattern is critical to the function of many hormones in order to maintain the delicate homeostatic balance necessary for essential life processes, such as development and reproduction. Variations of the concentration in a certain frequency can be critical to hormone function, as evidenced by the case of GnRH agonists, which cause functional inhibition of the receptor for GnRH due to profound downregulation in response to constant (tonic) stimulation. Pulsatility may function to sensitize target tissues to the hormone of interest and upregulate receptors, leading to improved responses. This heightened response may have served to improve the animal's fitness in its environment and promote its evolutionary retention.

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.
  7. Williams GR (April 2011). "Extrathyroidal expression of TSH receptor". Annales d'Endocrinologie. 54es Journees internationales d'Endocrinologie clinique. 72 (2): 68–73. doi:10.1016/j.ando.2011.03.006. PMID   21511243.
  8. Nakane Y, Yoshimura T (February 2019). "Photoperiodic Regulation of Reproduction in Vertebrates". Annual Review of Animal Biosciences. 7 (1): 173–194. doi:10.1146/annurev-animal-020518-115216. PMID   30332291.

Further reading