Parathyroid hormone
| Parathyroid hormone | |||||||||||
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| Symbols | PTH ; | ||||||||||
| External IDs | Template:OMIM5 Template:MGI HomoloGene: 266 | ||||||||||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Parathyroid hormone (PTH), or parathormone, is secreted by the parathyroid glands as a polypeptide containing 84 amino acids. It acts to increase the concentration of calcium (Ca2+) in the blood, whereas calcitonin (a hormone produced by the parafollicular cells (C cells) of the thyroid gland) acts to decrease calcium concentration. PTH acts to increase the concentration of calcium in the blood by acting upon parathyroid hormone receptor in three parts of the body:[1]
| Reference Range | |
| PTH | 1-7 pmol/l |
Functions
Effects on serum calcium (raising)
| Region | Effect |
| bones | It enhances the release of calcium from the large reservoir contained in the bones.[2] Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL, which can bind to osteoclast precursors containing RANK, a receptor for RANKL. The binding of RANKL to RANK stimulates these precursors to fuse, forming new osteoclasts which ultimately enhances the resorption of bone. |
| kidney | It enhances active reabsorption of calcium from distal tubules[3] and the thick ascending limb. |
| intestine via kidney | It enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D. Vitamin D activation occurs in the kidney. PTH up-regulates the enzyme responsible for 1-alpha hydroxylation of 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D). This actived form of vitamin D affects the absorption of calcium (as Ca2+ ions) by the intestine via calbindin. |
PTH was one of the first hormones to be shown to use the G-protein, adenylyl cyclase second messenger system.
Normal total plasma calcium level is 9.4mg/dl(8-11) or 2.4mmol/L[4] [5] .
Effects on serum phosphate (decrease, with compensation)
PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney[3] which means more phosphate is excreted through the urine.
However, PTH enhances the uptake of phosphate from the intestine and bones into the blood. In the bone, slightly more calcium than phosphate is released from the breakdown of bone. In the intestines, which is mediated by an increase in activated vitamin D, the absorption of phosphate is not as dependent on vitamin D as is that of calcium. The end result is a small net drop in the serum concentration of phosphate.
Feedback regulation
Increased calcium concentration in the blood acts (via feedback inhibition) to decrease PTH secretion by the parathyroid glands.
This is achieved by the activation of calcium-sensing receptors located on parathyroid cells.[6]
Differential Diagnosis
Increased
- Age
- Primary hyperparathyroidism
- Familial hypocalciuric hypercalcemia
- Familial hyperparathyroidism
- Gland hyperplasia
- Lithium therapy
- Parathyroid malignancy
- Osteomalacia
- Pseudohyperparathyroidism
- Ricketts
- Secondary hyperprathyroidism
- Vitamin D deficiency
Decreased
- Cancer
- Granulomatous
- PTH <2-20pg/ml and calcium <2.1mmol/l:Hypoparathyroidism
- PTH <2-20pg/ml and calcium >2.6mmol/l:hypercalcemia due to tumor
Syndromes
- A high level of PTH in the blood is known as hyperparathyroidism.
- If the cause is in the parathyroid gland it is called primary hyperparathyroidism. The causes are parathyroid adenoma, parathyroid hyperplasia and parathyroid cancer.
- If the cause is outside the gland, it is known as secondary hyperparathyroidism. This can occur in chronic renal failure.
- A low level of PTH in the blood is known as hypoparathyroidism. Causes include surgical misadventure (e.g. inadvertent removal during routine thyroid surgery), autoimmune disorder, and inborn errors of metabolism.
Measurements
PTH can be measured in the blood in several different forms: intact PTH; N-terminal PTH; mid-molecule PTH, and C-terminal PTH, and different tests are used in different clinical situations.
References
- ↑ Essentials of Human Physiology by Thomas M. Nosek. Section 5/5ch6/s5ch6_11.
- ↑ Poole K, Reeve J (2005). "Parathyroid hormone - a bone anabolic and catabolic agent". Curr Opin Pharmacol. 5 (6): 612–7. doi:10.1016/j.coph.2005.07.004. PMID 16181808.
- ↑ 3.0 3.1 http://sprojects.mmi.mcgill.ca/nephrology/presentation/presentation5.htm
- ↑ guyton
- ↑ http://books.google.com/books?id=BxLU6XhZsTAC&pg=RA1-PA281&lpg=RA1-PA281&dq=pth+second+messenger&source=web&ots=5awUECyZo-&sig=EhEGbV9WdI2Xp5Sv5eJQJ_63S3U#PRA1-PA281,M1
- ↑ Essentials of Human Physiology by Thomas M. Nosek. Section 5/5ch6/s5ch6_9.
See also
Further reading
- Drüeke TB, Massy ZA (2003). "Advanced oxidation protein products, parathyroid hormone and vascular calcification in uremia". Blood Purif. 20 (5): 494–7. PMID 12207101.
- Parfitt AM (2003). "Parathyroid hormone and periosteal bone expansion". J. Bone Miner. Res. 17 (10): 1741–3. PMID 12369776.
- Martin TJ (2004). "Does bone resorption inhibition affect the anabolic response to parathyroid hormone?". Trends Endocrinol. Metab. 15 (2): 49–50. PMID 15080150.
- Keutmann HT, Sauer MM, Hendy GN; et al. (1979). "Complete amino acid sequence of human parathyroid hormone". Biochemistry. 17 (26): 5723–9. PMID 728431.
- Keutmann HT, Niall HD, O'Riordan JL, Potts JT (1975). "A reinvestigation of the amino-terminal sequence of human parathyroid hormone". Biochemistry. 14 (9): 1842–7. doi:10.1021/bi00680a006. PMID 1125201.
- Parkinson DB, Thakker RV (1993). "A donor splice site mutation in the parathyroid hormone gene is associated with autosomal recessive hypoparathyroidism". Nat. Genet. 1 (2): 149–52. doi:10.1038/ng0592-149. PMID 1302009.
- Handt O, Reis A, Schmidtke J (1993). "Ectopic transcription of the parathyroid hormone gene in lymphocytes, lymphoblastoid cells and tumour tissue". J. Endocrinol. 135 (2): 249–56. PMID 1474331.
- Tonoki H, Narahara K, Matsumoto T, Niikawa N (1991). "Regional mapping of the parathyroid hormone gene (PTH) by cytogenetic and molecular studies". Cytogenet. Cell Genet. 56 (2): 103–4. PMID 1672845.
- Klaus W, Dieckmann T, Wray V; et al. (1991). "Investigation of the solution structure of the human parathyroid hormone fragment (1-34) by 1H NMR spectroscopy, distance geometry, and molecular dynamics calculations". Biochemistry. 30 (28): 6936–42. doi:10.1021/bi00242a018. PMID 2069952.
- Arnold A, Horst SA, Gardella TJ; et al. (1990). "Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism". J. Clin. Invest. 86 (4): 1084–7. doi:10.1172/JCI114811. PMID 2212001.
- Nussbaum SR, Gaz RD, Arnold A (1990). "Hypercalcemia and ectopic secretion of parathyroid hormone by an ovarian carcinoma with rearrangement of the gene for parathyroid hormone". N. Engl. J. Med. 323 (19): 1324–8. PMID 2215618.
- Ahn TG, Antonarakis SE, Kronenberg HM; et al. (1986). "Familial isolated hypoparathyroidism: a molecular genetic analysis of 8 families with 23 affected persons". Medicine (Baltimore). 65 (2): 73–81. PMID 3005800.
- Tregear GW, van Rietschoten J, Greene E; et al. (1975). "Solid-phase synthesis of the biologically active N-terminal 1 - 34 peptide of human parathyroid hormone". Hoppe-Seyler's Z. Physiol. Chem. 355 (4): 415–21. PMID 4474131.
- Niall HD, Sauer RT, Jacobs JW; et al. (1974). "The amino-acid sequence of the amino-terminal 37 residues of human parathyroid hormone". Proc. Natl. Acad. Sci. U.S.A. 71 (2): 384–8. doi:10.1073/pnas.71.2.384. PMID 4521809.
- Andreatta RH, Hartmann A, Jöhl A; et al. (1973). "[Synthesis of sequence 1-34 of human parathyroid hormone]". Helv. Chim. Acta. 56 (1): 470–3. doi:10.1002/hlca.19730560139. PMID 4721748.
- Jacobs JW, Kemper B, Niall HD; et al. (1974). "Structural analysis of human proparathyroid hormone by a new microsequencing approach". Nature. 249 (453): 155–7. doi:10.1038/249155a0. PMID 4833516.
- Vasicek TJ, McDevitt BE, Freeman MW; et al. (1983). "Nucleotide sequence of the human parathyroid hormone gene". Proc. Natl. Acad. Sci. U.S.A. 80 (8): 2127–31. doi:10.1073/pnas.80.8.2127. PMID 6220408.
- Mayer H, Breyel E, Bostock C, Schmidtke J (1983). "Assignment of the human parathyroid hormone gene to chromosome 11". Hum. Genet. 64 (3): 283–5. doi:10.1007/BF00279412. PMID 6885073.
- Hendy GN, Kronenberg HM, Potts JT, Rich A (1982). "Nucleotide sequence of cloned cDNAs encoding human preproparathyroid hormone". Proc. Natl. Acad. Sci. U.S.A. 78 (12): 7365–9. PMID 6950381.
- Hendy GN, Bennett HP, Gibbs BF; et al. (1995). "Proparathyroid hormone is preferentially cleaved to parathyroid hormone by the prohormone convertase furin. A mass spectrometric study". J. Biol. Chem. 270 (16): 9517–25. PMID 7721880.
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