Thyroglobulin

Last updated
TG
Identifiers
Aliases TG , AITD3, TGN, thyroglobulin
External IDs OMIM: 188450 MGI: 98733 HomoloGene: 2430 GeneCards: TG
Gene location (Human)
Ideogram human chromosome 8.svg
Chr. Chromosome 8 (human) [1]
Human chromosome 8 ideogram.svg
HSR 1996 II 3.5e.svg
Red rectangle 2x18.png
Band 8q24.22Start132,866,958 bp [1]
End133,134,903 bp [1]
RNA expression pattern
PBB GE CD44 204489 s at fs.png

PBB GE CD44 204490 s at fs.png

PBB GE CD44 212063 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003235

NM_009375

RefSeq (protein)

NP_003226

NP_033401

Location (UCSC) Chr 8: 132.87 – 133.13 Mb Chr 15: 66.67 – 66.85 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment of the thyroid follicles, accounting for approximately half of the protein content of the thyroid gland. [5] Human TG (hTG) is a homodimer of subunits each containing 2768 amino acids as synthesized (a short signal peptide of 19 aminoacids may be removed from the N-terminus in the mature protein). [6]

Contents

Thyroglobulin is in all vertebrates the main precursor to thyroid hormones, which are produced when thyroglobulin's tyrosine residues are combined with iodine and the protein is subsequently cleaved. Each thyroglobulin molecule contains approximately 100-120 tyrosine residues, but only a small number (20) of these are subject to iodination by thyroperoxidase in the follicular colloid. Therefore, each Tg molecule forms approximately 10 thyroid hormone molecules. [5]


Function

Thyroid hormone synthesis, this image traces thyroglobulin from production within the rough endoplasmic reticulum until proteolytic release of the thyroid hormones. Thyroid hormone synthesis.png
Thyroid hormone synthesis, this image traces thyroglobulin from production within the rough endoplasmic reticulum until proteolytic release of the thyroid hormones.

Thyroglobulin (Tg) acts as a substrate for the synthesis of the thyroid hormones thyroxine (T4) and triiodothyronine (T3), as well as the storage of the inactive forms of thyroid hormone and iodine within the follicular lumen of a thyroid follicle. [7]

Newly synthesized thyroid hormones (T3 and T4) are attached to thyroglobulin and comprise the colloid within the follicle. When stimulated by thyroid stimulating hormone (TSH), the colloid is endocytosed from the follicular lumen into the surrounding thyroid follicular epithelial cells. The colloid is subsequently cleaved by proteases to release thyroglobulin from its T3 and T4 attachments. [8]

The active forms of thyroid hormone: T3 and T4, are then released into circulation where they are either unbound or attached to plasma proteins, and thyroglobulin is recycled back into the follicular lumen where it can continue to serve as a substrate for thyroid hormone synthesis. [9]

Clinical significance

Half-life and clinical elevation

Metabolism of thyroglobulin occurs in the liver via thyroid gland recycling of the protein. Circulating thyroglobulin has a half-life of 65 hours. Following thyroidectomy, it may take many weeks before thyroglobulin levels become undetectable. Thyroglobulin levels may be tested regularly for a few weeks or months following the removal of the thyroid. [10] After thyroglobulin levels become undetectable (following thyroidectomy), levels can be serially monitored in follow-up of patients with papillary or follicular thyroid carcinoma.[ clarification needed ]

A subsequent elevation of the thyroglobulin level is an indication of recurrence of papillary or follicular thyroid carcinoma. In other words, a rise in thyroglobulin levels in the blood may be a sign that thyroid cancer cells are growing and/or the cancer is spreading. [10] Hence, thyroglobulin levels in the blood are mainly used as a tumor marker [11] [10] for certain kinds of thyroid cancer (particularly papillary or follicular thyroid cancer). Thyroglobulin is not produced by medullary or anaplastic thyroid carcinoma.

Thyroglobulin levels are tested via a simple blood test. Tests are often ordered after thyroid cancer treatment. [10]

Thyroglobulin antibodies

In the clinical laboratory, thyroglobulin testing can be complicated by the presence of anti-thyroglobulin antibodies (ATAs), alternatively referred to as TgAb. Anti-thyroglobulin antibodies are present in 1 in 10 normal individuals, and a greater percentage of patients with thyroid carcinoma. The presence of these antibodies can result in falsely low (or rarely falsely high) levels of reported thyroglobulin, a problem that can be somewhat circumvented by concomitant testing for the presence of ATAs. The ideal strategy for a clinician's interpretation and management of patient care in the event of confounding detection of ATAs is testing to follow serial quantitative measurements (rather than a single laboratory measurement).

ATAs are often found in patients with Hashimoto's thyroiditis or Graves' disease. Their presence is of limited use in the diagnosis of these diseases, since they may also be present in healthy euthyroid individuals. ATAs are also found in patients with Hashimoto's encephalopathy, a neuroendocrine disorder related to—but not caused by—Hashimoto's thyroiditis. [12]

Interactions

Thyroglobulin has been shown to interact with Binding immunoglobulin protein. [13] [14]

Related Research Articles

Thyroid Endocrine gland in the neck; secretes hormones that influence metabolism

The thyroid, or thyroid gland, is an endocrine gland in the neck consisting of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thyroid is located at the front of the neck, below the Adam's apple. Microscopically, the functional unit of the thyroid gland is the spherical thyroid follicle, lined with follicular cells (thyrocytes), and occasional parafollicular cells that surround a lumen containing colloid. The thyroid gland secretes three hormones: the two thyroid hormones – triiodothyronine (T3) and thyroxine (T4) – and a peptide hormone, calcitonin. The thyroid hormones influence the metabolic rate and protein synthesis, and in children, growth and development. Calcitonin plays a role in calcium homeostasis. Secretion of the two thyroid hormones is regulated by thyroid-stimulating hormone (TSH), which is secreted from the anterior pituitary gland. TSH is regulated by thyrotropin-releasing hormone (TRH), which is produced by the hypothalamus.

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.

Triiodothyronine chemical compound

Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate.

Thyroid follicular cell

Thyroid follicular cells are the major cell type in the thyroid gland, and are responsible for the production and secretion of the thyroid hormones thyroxine (T4) and triiodothyronine (T3). They form the single layer of cuboidal epithelium that makes up the outer structure of the almost spherical thyroid follicle.

Thyroid peroxidase enzyme

Thyroid peroxidase, also called thyroperoxidase (TPO) or iodide peroxidase, is an enzyme expressed mainly in the thyroid where it is secreted into colloid. Thyroid peroxidase oxidizes iodide ions to form iodine atoms for addition onto tyrosine residues on thyroglobulin for the production of thyroxine (T4) or triiodothyronine (T3), the thyroid hormones. In humans, thyroperoxidase is encoded by the TPO gene.

Papillary thyroid cancer thyroid carcinoma that is characterized by the small mushroom shape of the tumor which has a stem attached to the epithelial layer

Papillary thyroid cancer or papillary thyroid carcinoma is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases. It occurs more frequently in women and presents in the 20–55 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had previous radiation to the head and neck. It is often well-differentiated, slow-growing, and localized, although it can metastasize.

Midkine protein-coding gene in the species Homo sapiens

Midkine, also known as neurite growth-promoting factor 2 (NEGF2), is a protein that in humans is encoded by the MDK gene.

An antithyroid agent is a hormone antagonist acting upon thyroid hormones.

Diiodotyrosine chemical compound

Diiodotyrosine (DIT) is a precursor in the production of thyroid hormone, and results from iodization of monoiodotyrosine at the other meta- position on the phenol ring.

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.

G protein-coupled bile acid receptor protein-coding gene in the species Homo sapiens

The G protein-coupled bile acid receptor 1 (GPBAR1) also known G-protein coupled receptor 19 (GPCR19), membrane-type receptor for bile acids (M-BAR) or TGR5 as is a protein that in humans is encoded by the GPBAR1 gene.

PAX8 mammalian protein found in Homo sapiens

Paired box gene 8, also known as PAX8, is a protein which in humans is encoded by the PAX8 gene.

Dual oxidase 2 protein-coding gene in the species Homo sapiens

Dual oxidase 2, also known as DUOX2 or ThOX2, is an enzyme that in humans is encoded by the DUOX2 gene. Dual oxidase is an enzyme that was first identified in the mammalian thyroid gland. In humans, two isoforms are found; hDUOX1 and hDUOX2. The protein location is not exclusive to thyroid tissue; hDUOX1 is prominent in airway epithelial cells and hDUOX2 in the salivary glands and gastrointestinal tract.

Metallothionein 1G protein-coding gene in the species Homo sapiens

Metallothionein-1G is a protein that in humans is encoded by the MT1G gene.

Follicular thyroid cancer thyroid carcinoma that has material basis in follicular cells

Follicular thyroid cancer accounts for 15% of thyroid cancer and occurs more commonly in women over 50 years of age. Thyroglobulin (Tg) can be used as a tumor marker for well-differentiated follicular thyroid cancer. Thyroid follicular cells are the thyroid cells responsible for the production and secretion of thyroid hormones.

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.

Autoimmune thyroiditis, is a chronic disease in which the body interprets the thyroid glands and its hormone products T3, T4 and TSH as threats, therefore producing special antibodies that target the thyroid's cells, thereby destroying it.

Iodotyrosine deiodinase protein-coding gene in the species Homo sapiens

Iodotyrosine deiodinase, also known as iodotyrosine dehalogenase 1, is a type of deiodinase enzyme that scavenges iodide by removing it from iodinated tyrosine residues in the thyroid gland. These iodinated tyrosines are produced during thyroid hormone biosynthesis. The iodide that is scavenged by iodotyrosine deiodinase is necessary to again synthesize the thyroid hormones. After synthesis, the thyroid hormones circulate through the body to regulate metabolic rate, protein expression, and body temperature. Iodotyrosine deiodinase is thus necessary to keep levels of both iodide and thyroid hormones in balance.

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).

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an indolent thyroid tumor that was previously classified as an encapsulated follicular variant of papillary thyroid carcinoma, necessitating a new classification as it was recognized that encapsulated tumors without invasion have an indolent behavior, and may be over-treated if classified as a type of cancer.

References

Further reading

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000042832 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000053469 - 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. 1 2 Boron WF (2003). Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders. p. 1044. ISBN   1-4160-2328-3.
  6. ((cite web |url="https://www.ncbi.nlm.nih.gov/protein/NP_003226.4"))
  7. "TG thyroglobulin [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-09-16.
  8. Rousset, Bernard; Dupuy, Corinne; Miot, Françoise; Dumont, Jacques (2000), Feingold, Kenneth R.; Anawalt, Bradley; Boyce, Alison; Chrousos, George (eds.), "Chapter 2 Thyroid Hormone Synthesis And Secretion", Endotext, MDText.com, Inc., PMID   25905405 , retrieved 2019-09-17
  9. Rousset, Bernard; Dupuy, Corinne; Miot, Françoise; Dumont, Jacques (2000), Feingold, Kenneth R.; Anawalt, Bradley; Boyce, Alison; Chrousos, George (eds.), "Chapter 2 Thyroid Hormone Synthesis And Secretion", Endotext, MDText.com, Inc., PMID   25905405 , retrieved 2019-09-17
  10. 1 2 3 4 "Thyroglobulin: MedlinePlus Lab Test Information". medlineplus.gov. Retrieved 2019-05-06.
  11. "ACS :: Tumor Markers". American Cancer Society. Retrieved 2009-03-28.
  12. Ferracci F, Moretto G, Candeago RM, Cimini N, Conte F, Gentile M, Papa N, Carnevale A (February 2003). "Antithyroid antibodies in the CSF: Their role in the pathogenesis of Hashimoto's encephalopathy". Neurology. 60 (4): 712–4. doi:10.1212/01.wnl.0000048660.71390.c6. PMID   12601119.
  13. Delom F, Mallet B, Carayon P, Lejeune PJ (June 2001). "Role of extracellular molecular chaperones in the folding of oxidized proteins. Refolding of colloidal thyroglobulin by protein disulfide isomerase and immunoglobulin heavy chain-binding protein". J. Biol. Chem. 276 (24): 21337–42. doi: 10.1074/jbc.M101086200 . PMID   11294872.
  14. Delom F, Lejeune PJ, Vinet L, Carayon P, Mallet B (February 1999). "Involvement of oxidative reactions and extracellular protein chaperones in the rescue of misassembled thyroglobulin in the follicular lumen". Biochem. Biophys. Res. Commun. 255 (2): 438–43. doi:10.1006/bbrc.1999.0229. PMID   10049727.