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hormone secreted by the thyroid gland lowers blood calcium

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Amino acid peptide hormone secreted away parafollicular cells of the thyroid gland

CALCA
Calcitonin.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases CALCA, CALC1, CGRP, CGRP-I, CGRP1, Computerized axial tomography, KC, PCT, calcitonin related polypeptide alpha, CGRP-alpha
External IDs OMIM: 114130 HomoloGene: 88401 GeneCards: CALCA
Orthologs
Species Human Shiner
Entrez

796

n/a
Ensembl

ENSG00000110680

n/a
UniProt

P06881

n/a
RefSeq (mRNA)

NM_001033952
NM_001033953
NM_001741
NM_001378949
NM_001378950

n/a

RefSeq (protein)

NP_001029125.1

n/a

Location (UCSC) Chr 11: 14.97 – 14.97 Mb n/a
PubMed search [2] n/a
Wikidata
View/Redact Human

Thyrocalcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (alias C cells) of the thyroid gland in world, and in many other animals in the ultimopharyngeal body.[3] It acts to keep down blood calcium (Ca2+), opposed the effects of parathyroid gland endocrine (PTH).[4]

Calcitonin has been found in fish, reptiles, birds, and mammals. Its grandness in humans has non been as well legitimate as its importance in other animals, as its function is usually not significant in the regulation of normal calcium homeostasis.[5] It belongs to the calcitonin-care protein family.

Historically calcitonin has also been known as thyrocalcitonin.

Biosynthesis and regularization [delete]

Calcitonin is formed aside the chemical change cleavage of a larger prepropeptide, which is the product of the CALC1 gene (CALCA). It is functionally an antagonist with PTH and Vitamin D3.The CALC1 gene belongs to a superfamily of related protein hormone precursors including islet amyloid forerunner protein, thyrocalcitonin gene-kindred peptide, and the precursor of adrenomedullin.

Secretion of calcitonin is stimulated by:

  • an growth in blood serum [California2+][6]
  • gastrin and pentagastrin.[7]

Function [edit]

The hormone participates in calcium (Atomic number 202+) and phosphorus metamorphosis. In many slipway, thyrocalcitonin counteracts parathormone (PTH) and D.

More specifically, thyrocalcitonin lowers lineage Ca2+ levels in two ways:

  • Major effect: Inhibits osteoclast activity in bones, which give out the bone[8]
  • Minor effect: Inhibits urinary organ tubular cell reabsorption of Ca2+ and phosphate, allowing them to follow excreted in the urine[9] [10]

High concentrations of calcitonin may exist able to increase urinary excretion of calcium and phosphate via the renal tubules.[11] directive to marked hypocalcemia. However, this is a minor effect with no physiological signification in humans. It is besides a squab-lived effect because the kidneys become defiant to calcitonin, as demonstrated by the kidney's unaffected excretion of atomic number 20 in patients with thyroid tumors that secrete excessive thyrocalcitonin.[12]

In its skeleton-preserving actions, calcitonin protects against calcium loss from the skeleton during periods of calcium mobilization, such as maternity and, especially, lactation. The protective mechanisms include the direct inhibition of mug up reabsorption and the hearsay effect through the forbiddance of the discharge of prolactin from the pituitary gland. The reason provided is that prolactin induces the release of PTH consanguine peptide which enhances bone resorption, merely is still under investigating.,[13] [14] [15]

Other effects are in preventing postprandial hypercalcemia resulting from preoccupation of Ca2+. Also, thyrocalcitonin inhibits food ingestion in rats and monkeys, and may have CNS action involving the regulation of feeding and appetite.

Calcitonin lowers blood calcium and phosphorus mainly through and through its inhibition of osteoclasts. Osteoblasts do not have calcitonin receptors and are therefore not directly affected by calcitonin levels. However, since bony resorption and cram formation are linked processes, yet calcitonin's inhibition of osteoclastic activity leads to increased osteoblastic activity (As an indirect force).[12]

Receptor [edit]

The calcitonin sensory receptor is a G protein-coupled receptor localized to osteoclasts[16] as well kidney and brain cells. IT is coupled to a Gsα subunit, so moving cAMP production by adenylate cyclase in target cells. It may also bear upon the ovaries in women and the testes in manpower.[ citation needed ]

Discovery [edit]

Calcitonin was first purified in 1962 away Douglas Harold Copp and B. Cheney at the University of British Columbia, Canada.[17] IT was initially thought to be secreted past the parathyroid secreter but was shown by Iain Macintyre and his team at the Royal Postgraduate School of medicine, London, to be secreted past parafollicular cells of the thyroid gland.[18] Dr. Copp named the determined hormone thyrocalcitonin because of its role in 'maintaining mean calcium chant'.[17]

Medical import [cut]

Calcitonin assay is used in identifying patients with nodular thyroid diseases. IT is helpful in making an early diagnosis of medullary carcinoma of thyroid. A malignancy of the parafollicular cells, i.e. Medullary thyroid cancer, typically produces an elevated railroad blood serum calcitonin level. Prognosis of MTC depends on archaean detection and treatment.

Calcitonin also has importantly compact molecular biology, as the gene encoding calcitonin was the first gene discovered in mammalian cells to be alternatively spliced, now known to beryllium a ubiquitous mechanism in eukaryotes.[19] [20]

Pharmacology [edit]

Thyrocalcitonin has clinically been used for metabolic bone up disorders for much than 50 years.[21] Salmon calcitonin is used for the discourse of:

  • Postmenopausal osteoporosis[22]
  • Hypercalcemia[23]
  • Bone metastases[24]
  • Sir James Paget's disease[25]
  • Phantom limb pain[26]

It has been investigated as a attainable not-operative treatment for spinal stenosis.[27]

The pursuit information is from the GB Electronic Medicines Collection[28]

General characteristics of the active substance [edit out]

Salmon calcitonin is rapidly absorbed and eliminated. Peak plasma concentrations are attained inside the first hour of organization.

Animal studies have shown that calcitonin is primarily metabolised via proteolysis in the kidney succeeding parenteral presidency. The metabolites lack the specific biological activity of calcitonin. Bioavailability succeeding body covering and intramuscular shot in humans is high and correspondent for the two routes of organization (71% and 66%, respectively).

Calcitonin has short absorption and liquidation fractional-lives of 10–15 proceedings and 50–80 transactions, respectively. Salmon calcitonin is primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. Therefore, the metabolic clearance is much lower in patients with last-stage kidney failure than in healthy subjects. However, the clinical relevance of this finding is non known. Plasma protein binding is 30% to 40%.

Characteristics in patients [edit]

There is a relationship between the subcutaneous dose of calcitonin and peak plasma concentrations. Following parenteral administration of 100 IU calcitonin, peak plasma assiduousness lies between about 200 and 400 pg/cubic centimeter. Higher blood levels English hawthorn be associated with increased relative incidence of nausea, regurgitation, and secretory diarrhea.

Preclinical safety data [edit]

Schematic long-run toxicity, reproduction, mutagenicity, and carcinogenicity studies have been performed in laboratory animals. Salmon calcitonin is devoid of embryotoxic, teratogenic, and mutagenic potential.

An increased relative incidence of pituitary adenomas has been reported in rats given synthetic chromatic calcitonin for 1 class. This is considered a species-specialized effect and of no clinical relevance.[29] Salmon thyrocalcitonin does not cross the placental barrier.

In lactating animals given calcitonin, suppression of milk production has been observed. Calcitonin is secreted into the milk.

Pharmaceutical fabricate [edit]

Calcitonin was extracted from the ultimobranchial glands (thyroid-like glands) of fish, peculiarly salmon. Salmon calcitonin resembles frail calcitonin, but is more active. At present, it is produced either by recombinant DNA technology operating theater by natural science peptide synthesis. The pharmacological properties of the synthetic and recombinant peptides accept been incontestable to be qualitatively and quantitatively equivalent weight.[28]

Uses of calcitonin [edit]

Treatments [edit]

Calcitonin affecting the spine.

Calcitonin tin be used therapeutically for the discourse of hypercalcemia or osteoporosis.[30] In a Holocene clinical read, hypodermic injections of calcitonin have remittent the incidence of fractures and reduced the decrement in bone aggregate in women with type 2 diabetes complicated with osteoporosis.[31]

Subcutaneous injections of calcitonin in patients suffering from manic disorder resulted in significant decreases in irritability, euphoria and hyperactivity and hence calcitonin holds promise for treating bipolar disorder.[32] However no encourage process this expected coating of calcitonin has been reported.

Diagnostics [edit]

It may comprise used diagnostically as a tumor marker for medullary thyroid malignant neoplastic disease, in which high calcitonin levels English hawthorn be present and elevated levels after operating room may indicate return. It may flatbottom be utilised on biopsy samples from suspicious lesions (e.g., lymph nodes that are swollen) to establish whether they are metastases of the seminal cancer.

Cutoffs for calcitonin to identify cases with medullary thyroidal Cancer the Crab have been suggested to be as follows, with a higher value increasing the mistrust of medullary thyroid cancer:[33]

  • females: 5 nanogram/L or pg/mL
  • males: 12 ng/L or pg/mL
  • children under 6 months of age: 40 nanogram/L or pg/millilitre
  • children between 6 months and 3 years of age: 15 nanogram/L OR pg/mL

When over 3 age of age, full-grown cutoffs may comprise exploited

Increased levels of calcitonin have likewise been reportable for various other conditions. They let in: C-cell hyperplasia, nonthyroidal oat cell carcinoma, nonthyroidal carcinoma and other nonthyroidal malignancies, acute kidney injury and chronic kidney failure, hypercalcaemia, hypergastrinemia, and other gastrointestinal disorders, and pulmonary disease.[34]

Structure [edit]

Thyrocalcitonin is a polypeptide hormone of 32 paraffin acids, with a unit weightiness of 3454.93 daltons. Its structure comprises a single alpha helix.[35] Alternative splicing of the gene coding for calcitonin produces a distantly related peptide of 37 amino acids, called thyrocalcitonin gene-related peptide (CGRP), important type.[36]

The following are the amino acid sequences of salmon and human calcitonin:[ citation needed ] [37]

  • salmon:

Cys-Ser-Asn-Leu-Ser-Thr-Cys-Val-Leu-Gly-Lys-Leu-Ser-Gln-Glu-Leu-His-Lys-Leu-Gln-Thr-Tyr-Pro-Arg-Thr-Asn-Thr-Gly-Ser-Gly-Thr-Pro

  • human:

Cys-Gly-Asn-Leu-Ser-Thr-Cys-Met-Leu-Gly-Thr-Tyr-Thr-Gln-Asp-Phe-Asn-Lys-Phe-His-Thr-Phe-Pro-Gln-Thr-Ala-Ile-Gly-Val-Gly-Ala-Pro

Compared to salmon thyrocalcitonin, human calcitonin differs at 16 residues.

Research [edit]

In addition to the injectable and nasal spray dosage forms of the Salmon calcitonin, noninvasive oral formulations of the peptide are currently below clinical development. The short-half life of this peptide in serum triggered respective attempts to enhance plasma concentrations. The peptide is complexed with a macromolecule that Acts as an absorption foil through the transcellular tract and, additionally, protects the peptide from the plush-like pH and enzymatic conditions of the Gastrointestinal tract. This complexation is weak, noncovalent and reversible and the drug remains chemically unrestricted. After enactment through the intestine, the delivery agent dissociates from the peptide. Nonpareil of the extensively studied oral formulations is the disodium salts of 5-CNAC spoken calcitonin. This new viva voce program in a number of clinical trials at different phases has demonstrated promising enhanced pharmacokinetic profile, high bioavailability, well-established safety and comparable efficaciousness thereto of nasal calcitonin especially for treatment of biological time bone loss.[21]

See besides [edit]

  • Procalcitonin

References [edit]

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  2. ^ "Human PubMed Reference:". Home Center for Ergonomics Entropy, U.S. National Library of Medicine.
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  4. ^ Boron WF, Boulpaep EL (2004). "Gland system chapter". Medical Physiology: A Cellular And Molecular Plan of attack. Elsevier/Saunders. ISBN1-4160-2328-3.
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  6. ^ Costanzo, Linda S. (2007). BRS Physiology . Lippincott, Williams, &adenosine monophosphate; Maurice Wilkins. pp. 263. ISBN978-0-7817-7311-9.
  7. ^ Erdogan MF, Gursoy A, Kulaksizoglu M (October 2006). "Recollective-term personal effects of elevated gastrin levels on calcitonin secretion". J. Endocrinol. Adorn. 29 (9): 771–5. doi:10.1007/BF03347369. PMID 17114906. S2CID 41798141.
  8. ^ Costoff A. "Religious sect. 5, Ch. 6: Personal effects of CAT happening Debone". Medical College of Georgia. Archived from the original connected June 22, 2008. Retrieved 2008-08-07 .
  9. ^ Potts J, Jüppner H (2008). "Chapter 353. Disorders of the Parathyroid gland Gland and Calcium Homeostasis". In Longo DL, Kasper Deciliter, Jameson JL, Fauci Arsenic, Hauser SL, Loscalzo J (eds.). Benjamin Harrison's Principles of Internal Medicine (18th ED.). McGraw-Hill. Archived from the original on 2017-05-08. Retrieved 2017-05-29 .
  10. ^ Rhoades R (2009). Medical Physiology: Principles for Clinical Medicine. Philadelphia: Lippincott Williams & Wilkins. ISBN978-0-7817-6852-8.
  11. ^ Carney SL (1997). "Calcitonin and earthborn renal atomic number 20 and electrolyte transport". Mineral and Electrolyte Metabolism. 23 (1): 43–7. PMID 9058369.
  12. ^ a b Goodman HM (2009). Basic Medical examination Endocrinology (Quartern ed.). Elsevier. ISBN978-0-12-373975-9.
  13. ^ Horwitz MJ, Tedesco Megabyte, Sereika SM, Syed MA, Garcia-Ocaña A, Bisello A, Hollis BW, Rosen CJ, Wysolmerski JJ, Dann P, Gundberg C, Stewart AF (October 2005). "Continuous PTH and PTHrP infusion causes crushing of bone formation and discordant effects on 1,25(Ohio)2 vitamin D". J. Bone Miner. RES. 20 (10): 1792–803. doi:10.1359/JBMR.050602. PMID 16160737. S2CID 25594820.
  14. ^ Davey RA, Henry Hubert Turner AG, McManus JF, Chiu WS, Tjahyono F, Moore AJ, Atkins GJ, Anderson PH, Mom C, Glatt V, MacLean He, Vincent C, Bouxsein M, Morris HA, Findlay Decimetre, Zajac JD (August 2008). "Calcitonin receptor plays a physiologic office to protect against hypercalcemia in mice". J. Bone Miner. Res. 23 (8): 1182–93. doi:10.1359/jbmr.080310. PMC2680171. PMID 18627265.
  15. ^ Woodrow JP, Sharpe CJ, Parry New Jersey, Hoff AO, Gagel RF, Kovacs CS (Sep 2006). "Thyrocalcitonin plays a critical persona in regulating skeletal mineral metabolic process during lactation". Endocrinology. 147 (9): 4010–21. doi:10.1210/nut.2005-1616. PMID 16675524.
  16. ^ Nicholson GC, Moseley JM, Sexton Postmortem examination, Mendelsohn FA, Martin TJ (Revered 1986). "Abundant calcitonin receptors in isolated rat osteoclasts. Biochemical and skiagraphy portrayal". J. Clin. Invest. 78 (2): 355–60. doi:10.1172/JCI112584. PMC423551. PMID 3016026.
  17. ^ a b Copp DH, Cheney B (January 1962). "Thyrocalcitonin-a hormone from the parathyroid which lowers the calcium-steady of the blood". Nature. 193 (4813): 381–2. Bibcode:1962Natur.193..381C. Interior:10.1038/193381a0. PMID 13881213. S2CID 4292938.
  18. ^ Foster GV, Baghdiantz A, Kumar MA, Falling of E, Soliman HA, Macintyre I (June 1964). "Thyroid origin of calcitonin". Nature. 202 (4939): 1303–5. Bibcode:1964Natur.202.1303F. DoI:10.1038/2021303a0. PMID 14210962. S2CID 2443410.
  19. ^ Rosenfeld MG, Amara SG, Roos BA, Ong ES, Herbert McLean Evans RM (March 1981). "Altered saying of the calcitonin gene related with RNA polymorphism". Nature. 290 (5801): 63–5. Bibcode:1981Natur.290...63R. doi:10.1038/290063a0. PMID 7207587. S2CID 4318349.
  20. ^ Rosenfeld MG, Lin CR, Amara SG, Stolarsky L, Roos BA, Ong ES, Evans RM (March 1982). "Calcitonin mRNA polymorphism: peptide shift associated with alternative RNA splicing events". Transactions of the National Academy of Sciences of the US Government of America. 79 (6): 1717–21. Bibcode:1982PNAS...79.1717R. doi:10.1073/pnas.79.6.1717. PMC346051. PMID 6952224.
  21. ^ a b das Neves, José; Sarmento, Bruno (2014). Tissue layer Delivery of Biopharmaceuticals. Boston, Bay State: Springer US. p. 407- 422. doi:10.1007/978-1-4614-9524-6_18. ISBN978-1-4614-9524-6.
  22. ^ "Handout on Health: Osteoporosis". NIAMS. August 2014. Archived from the original on 18 May 2015. Retrieved 16 May 2015.
  23. ^ "Hypercalcemia". The Lecturio Graeco-Roman deity Construct Subroutine library . Retrieved 1 October 2021.
  24. ^ MedlinePlus Overview bonecancer
  25. ^ "Paget's Disease of Bone". The Lecturio Medical Concept Library . Retrieved 1 October 2021.
  26. ^ Wall GHz, Heyneman CA (April 1999). "Calcitonin in phantom limb pain". The Chronological record of Pharmacotherapy. 33 (4): 499–501. DoI:10.1345/aph.18204. PMID 10332543. S2CID 30651328.
  27. ^ Tran DQ, Duong S, Finlayson RJ (July 2010). "Body part spinal anesthesia stricture: a short review of the nonsurgical direction". Can J Anaesth. 57 (7): 694–703. doi:10.1007/s12630-010-9315-3. PMID 20428988.
  28. ^ a b "Lepton Medicines Collection". Archived from the original on 2005-11-08. Retrieved 2008-08-07 .
  29. ^ "Injectable Salmon Thyrocalcitonin" (PDF).
  30. ^ Inzerillo AM, Zaidi M, Huang CL (2004). "Calcitonin: physiological actions and clinical applications". Journal of Pediatric Endocrinology & Metabolism. 17 (7): 931–40. doi:10.1007/s00198-015-3149-3. PMID 15301040. S2CID 23551343.
  31. ^ Dexue L, Yueyue Z (November 2014). "Salmon thyrocalcitonin in the handling of elderly women with type 2 diabetes complicated with osteoporosis". Pak J Pharm Sci. 27 (6 Suppl): 2079–81. PMID 25410076.
  32. ^ Vik A, Yatham LN (March on 1998). "Calcitonin and bipolar unhinge: a hypothesis revisited". Journal of Psychiatry & Neuroscience. 23 (2): 109–17. PMC1188909. PMID 9549251.
  33. ^ Basuyau JP, Beetle E, Leroy M, Brunelle P (October 2004). "Reference intervals for serum calcitonin in men, women, and children". Clin. Chem. 50 (10): 1828–30. DoI:10.1373/clinchem.2003.026963. PMID 15388660.
  34. ^ Burtis CA, Ashwood ER, Bruns Diamond State (2012). Tietz Text edition of Medical institution Chemistry and Molecular Nosology (5th ed.). Elsevier Saunders. p. 1774. ISBN978-1-4160-6164-9.
  35. ^ Andreotti G, Méndez BL, Amodeo P, Morelli MA, Nakamuta H, Motta A (August 2006). "Structural determinants of salmon calcitonin bioactivity: the role of the Leu-supported amphipathic alpha-helix". J. Biol. Chem. 281 (34): 24193–203. doi:10.1074/jbc.M603528200. PMID 16766525.
  36. ^ "thyrocalcitonin domain annotation". SMART (a Simple Standard Architecture Research Tool). embl-heidelberg.de. Retrieved 2009-02-22 .
  37. ^ "Salmon calicitonin". prospecbio.

Further reading material [edit]

  • MacIntyre I, Alevizaki M, Bevis PJ, Zaidi M (April 1987). "Calcitonin and the peptides from the calcitonin gene". Clinical Orthopaedics and Related Enquiry. 217 (217): 45–55. doi:10.1097/00003086-198704000-00007. PMID 3549095.
  • Di Angelantonio S, Giniatullin R, Costa V, Sokolova E, Nistri A (July 2003). "Modulation of neuronal nicotinic receptor function by the neuropeptides CGRP and substance P along autonomic nerve cells". British people Journal of Pharmacology. 139 (6): 1061–73. Department of the Interior:10.1038/sj.bjp.0705337. PMC1573932. PMID 12871824.
  • Findlay Decimeter, Sexton PM (December 2004). "Calcitonin". Emergence Factors. 22 (4): 217–24. Interior Department:10.1080/08977190410001728033. PMID 15621724. S2CID 218910711.
  • Sponholz C, Sakr Y, Reinhart K, Brunkhorst F (2007). "Characteristic value and prognostic implications of blood serum procalcitonin after viscus OR: a organized review of the literature". Critical Care. 10 (5): R145. doi:10.1186/cc5067. PMC1751067. PMID 17038199.
  • Schneider Hydrargyrum, Lam QT (August 2007). "Procalcitonin for the clinical laboratory: a review". Pathology. 39 (4): 383–90. doi:10.1080/00313020701444564. PMID 17676478. S2CID 28018130.
  • Grani G, Nesca A, Del Sordo M, Calvanese A, Carbotta G, Bianchini M, Fumarola A (June 2012). "Interpretation of serum calcitonin in patients with chronic autoimmune thyroiditis". Endocrine-Related Cancer. Bioscientifica. 19 (3): 345–9. doi:10.1530/ERC-12-0013. PMID 22399011.

External links [edit]

  • The Calcitonin Protein
  • Calcitonin at the US United States National Library of Medicine Medical Subject Headings (MeSH)

hormone secreted by the thyroid gland lowers blood calcium

Source: https://en.wikipedia.org/wiki/Calcitonin

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