Parathyroid hormone-related protein
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Overview
Parathyroid hormone-related protein (or PTHrP) is a protein member of the parathyroid hormone family. It is occasionally secreted by cancer cells (breast cancer, certain types of lung cancer including squamous cell carcinoma). However, it also has normal functions.
Functions
PTHrP acts as an endocrine, autocrine/ paracrine, and intracrine hormone. It regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. It aids in normal mammary gland development and lactation, possibly by regulating the mobilization and transfer of calcium to the milk, as well as placental transfer of calcium.
PTHrP is related in function to the "normal" parathyroid hormone. When a tumor secretes PTHrP, this can lead to hypercalcemia. As this is sometimes the first sign of the malignancy, hypercalcemia caused by PTHrP is considered a paraneoplastic phenomenon.
PTHrP shares the same N-terminal end as parathyroid hormone and therefore it can bind to the same receptor, the Type I PTH receptor (PTHR1). PTHR1 is responsible for most cases of humoral hypercalcemia of malignancy.
Genetics
Four alternatively spliced transcript variants encoding two distinct isoforms have been observed. There is also evidence for alternative translation initiation from non-AUG (CUG and GUG) start sites, in-frame and downstream of the initiator AUG codon, to give rise to nuclear forms of this hormone.[1]
History
The protein was first isolated in 1988 by Broadus et al. Miao et al showed that disruption of the PTHrP gene in mice caused a lethal phenotype and distinct bone abnormalities, suggesting that PTHrP has a physiological function.
References
Further reading
- Broadus AE, Mangin M, Ikeda K, Insogna KL, Weir EC, Burtis WJ, Stewart AF. Humoral hypercalcemia of cancer. Identification of a novel parathyroid hormone-like peptide. N Engl J Med 1988;319:556-63. PMID 3043221.
- Miao D, Li J, Xue Y, Su H, Karaplis AC, Goltzman D. Parathyroid hormone-related peptide is required for increased trabecular bone volume in parathyroid hormone-null mice. Endocrinology 2004;145:3554-62. PMID 15090463.
- Casey ML, MacDonald PC (1997). "The endothelin-parathyroid hormone-related protein vasoactive peptide system in human endometrium: modulation by transforming growth factor-beta.". Hum. Reprod. 11 Suppl 2: 62-82. PMID 8982748.
- Lam MH, Thomas RJ, Martin TJ, et al. (2000). "Nuclear and nucleolar localization of parathyroid hormone-related protein.". Immunol. Cell Biol. 78 (4): 395-402. doi:10.1046/j.1440-1711.2000.00919.x. PMID 10947864.
- Fiaschi-Taesch NM, Stewart AF (2003). "Minireview: parathyroid hormone-related protein as an intracrine factor--trafficking mechanisms and functional consequences.". Endocrinology 144 (2): 407-11. doi:10.1210/en.2002-220818. PMID 12538599.
- Jans DA, Thomas RJ, Gillespie MT (2003). "Parathyroid hormone-related protein (PTHrP): a nucleocytoplasmic shuttling protein with distinct paracrine and intracrine roles.". Vitam. Horm. 66: 345-84. PMID 12852260.
- Maioli E, Fortino V, Pacini A (2005). "Parathyroid hormone-related protein in preeclampsia: a linkage between maternal and fetal failures.". Biol. Reprod. 71 (6): 1779-84. doi:10.1095/biolreprod.104.030932. PMID 15286039.
- Fenton AJ, Kemp BE, Kent GN, et al. (1991). "A carboxyl-terminal peptide from the parathyroid hormone-related protein inhibits bone resorption by osteoclasts.". Endocrinology 129 (4): 1762-8. PMID 1915066.
- Fenton AJ, Kemp BE, Hammonds RG, et al. (1991). "A potent inhibitor of osteoclastic bone resorption within a highly conserved pentapeptide region of parathyroid hormone-related protein; PTHrP[107-111]". Endocrinology 129 (6): 3424-6. PMID 1954916.
- Moniz C, Burton PB, Malik AN, et al. (1991). "Parathyroid hormone-related peptide in normal human fetal development.". J. Mol. Endocrinol. 5 (3): 259-66. PMID 2288637.
- Hammonds RG, McKay P, Winslow GA, et al. (1989). "Purification and characterization of recombinant human parathyroid hormone-related protein.". J. Biol. Chem. 264 (25): 14806-11. PMID 2549037.
- Yasuda T, Banville D, Hendy GN, Goltzman D (1989). "Characterization of the human parathyroid hormone-like peptide gene. Functional and evolutionary aspects.". J. Biol. Chem. 264 (13): 7720-5. PMID 2708388.
- Suva LJ, Mather KA, Gillespie MT, et al. (1989). "Structure of the 5' flanking region of the gene encoding human parathyroid-hormone-related protein (PTHrP).". Gene 77 (1): 95-105. doi:10.1016/0378-1119(89)90363-6. PMID 2744490.
- Mangin M, Webb AC, Dreyer BE, et al. (1988). "Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with humoral hypercalcemia of malignancy.". Proc. Natl. Acad. Sci. U.S.A. 85 (2): 597-601. doi:10.1073/pnas.85.2.597. PMID 2829195.
- Moseley JM, Kubota M, Diefenbach-Jagger H, et al. (1987). "Parathyroid hormone-related protein purified from a human lung cancer cell line.". Proc. Natl. Acad. Sci. U.S.A. 84 (14): 5048-52. doi:10.1073/pnas.84.14.5048. PMID 2885845.
- Mangin M, Ikeda K, Dreyer BE, Broadus AE (1989). "Isolation and characterization of the human parathyroid hormone-like peptide gene.". Proc. Natl. Acad. Sci. U.S.A. 86 (7): 2408-12. doi:10.1073/pnas.86.7.2408. PMID 2928340.
- Thiede MA, Strewler GJ, Nissenson RA, et al. (1988). "Human renal carcinoma expresses two messages encoding a parathyroid hormone-like peptide: evidence for the alternative splicing of a single-copy gene.". Proc. Natl. Acad. Sci. U.S.A. 85 (13): 4605-9. doi:10.1073/pnas.85.13.4605. PMID 3290897.
- Suva LJ, Winslow GA, Wettenhall RE, et al. (1987). "A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression.". Science 237 (4817): 893-6. doi:10.1126/science.3616618. PMID 3616618.
- Campos RV, Zhang L, Drucker DJ (1995). "Differential expression of RNA transcripts encoding unique carboxy-terminal sequences of human parathyroid hormone-related peptide.". Mol. Endocrinol. 8 (12): 1656-66. PMID 7708054.
- Holick MF, Ray S, Chen TC, et al. (1994). "A parathyroid hormone antagonist stimulates epidermal proliferation and hair growth in mice.". Proc. Natl. Acad. Sci. U.S.A. 91 (17): 8014-6. doi:10.1073/pnas.91.17.8014. PMID 8058749.
- Seitz PK, Cooper KM, Ives KL, et al. (1993). "Parathyroid hormone-related peptide production and action in a myoepithelial cell line derived from normal human breast.". Endocrinology 133 (3): 1116-24. doi:10.1210/en.133.3.1116. PMID 8396010.
- Li H, Seitz PK, Selvanayagam P, et al. (1996). "Effect of endogenously produced parathyroid hormone-related peptide on growth of a human hepatoma cell line (Hep G2).". Endocrinology 137 (6): 2367-74. doi:10.1210/en.137.6.2367. PMID 8641188.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
