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PTH  -  parathyroid hormone

Homo sapiens

Synonyms: PTH1, Parathormone, Parathyrin, Parathyroid hormone
 
 
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Disease relevance of PTH

  • The data provide one possible pathway for the participation of excess PTH in the genesis of the anemia of uremia [1].
  • Less severe vitamin D deficiency causes an increase of serum PTH leading to bone resorption, osteoporosis and fractures [2].
  • Immunohistochemically, there were two different types of adenoma cells, i.e., one positive only for PTH and the other positive for both PTH and PTHrP [3].
  • Furthermore, the PTH 1-84 secretory response to EGTA-induced acute and severe hypocalcemia was significantly inhibited by PTH 7-84 [4].
  • To address this issue in humans, bone biopsy specimen samples from 9 normal controls and 16 patients with moderate to severe secondary renal hyperparathyroid bone disease (2 degrees HPT) with elevated PTH levels were studied to determine whether osteoclasts in the bone microenvironment express PTH-1R messenger RNA (mRNA) and protein [5].
  • While hypoparathyroidism develops after TT plus ND, little is known of postoperative PTH response [6].
 

Psychiatry related information on PTH

 

High impact information on PTH

 

Chemical compound and disease context of PTH

 

Biological context of PTH

 

Anatomical context of PTH

  • Expression of RANKL mRNA in osteoblasts/stromal cells is up-regulated by osteotropic factors such as 1 alpha, 25(OH)2D3, PTH, and IL-11 [23].
  • Intact PTH (1-84 bPTH) in concentrations (7.5-30 U/ml;) comparable to those found in blood of uremic patients produced marked and significant (P less than 0.01) inhibition of BFU-E and mouse marrow GFU-GM, but not of mouse marrow CFU-E [1].
  • In osteoblasts, RANKL expression is regulated by two major calcemic hormones, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and parathyroid hormone (PTH), as well as by several inflammatory/osteoclastogenic cytokines; the molecular mechanisms for this regulation are unclear [24].
  • Primary hyperparathyroidism is a common endocrine disorder caused by parathyroid gland enlargement and excessive parathyroid hormone (PTH) secretion [25].
  • NCD14+ monocytes also differentiated into osteoclasts in PTH-treated cocultures with SaOS-4/3 cells [26].
 

Associations of PTH with chemical compounds

  • We conclude that PTH and PLP activate adenylate cyclase by binding to common receptors in bone and kidney [27].
  • Desensitization by hPTH did not affect responses to either InsP3 or serotonin, but cells desensitized to injected InsP3 still responded strongly to PTH [28].
  • Oocytes did not respond to either cADPR or NAADP+, but NADP+ and analogues were found to be potent inhibitors of PTH signaling [28].
  • Interestingly, OA osteoblasts produced more prostaglandin E2 (PGE2) than normal osteoblasts, and using naproxen, a cyclo-oxygenase inhibitor, increased PTH-dependent cAMP formation to a level similar to normal osteoblasts [29].
  • Despite the reduction of plasma Ca(2+), no stimulation of PTH 1-84 secretion took place [4].
 

Physical interactions of PTH

  • Likewise, PLP peptides and bPTH-(1-34) were equipotent in competing with 125I-bPTH-(1-34) for binding to PTH receptors in renal membranes [27].
  • Synthetic hPTH (1-84) was found to be highly potent in binding to PTH receptors (Kb = 1-25 nM) and stimulating adenylate cyclase (Km = 1-14 nM) [30].
  • PTH-stimulated cyclic adenosine monophosphate (cAMP) generation was determined by radioimmunoassay (RIA), PTH binding and PTH1R mRNA levels were determined by radioligand binding and Northern analysis, respectively [31].
  • G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells [32].
  • The receptor for parathyroid hormone and parathyroid hormone-related peptide is hydrolyzed and its signaling properties are altered by directly binding the calpain small subunit [33].
  • We conclude that whereas PTH and PTHrP bind similarly to the G protein-coupled PTHR conformation (RG), PTH has a greater capacity to bind to the G protein-uncoupled conformation (R(0)) and, hence, can produce cumulatively greater signaling responses (via R(0)-->RG isomerization) than can PTHrP [34].
 

Enzymatic interactions of PTH

  • We also showed that a synthetic peptide comprising the -6 to +7 sequence of human pro-PTH is appropriately cleaved by purified furin in vitro [35].
  • When serine residues at positions 483, 485, 486, 489, 495, and 498 were simultaneously replaced by alanine residues, the PTH receptor was no longer phosphorylated either basally or in response to PTH [36].
  • CONCLUSION: These data suggest that NaPi-IIa and PTH-induced phosphorylated proteins that include ezrin are compartmentalized in LDM microdomains [37].
  • METHODS: We examined the submembrane localization of NaPi-IIa in opossum kidney (OK-N2) cells that stably expressed human NaPi-IIa, and searched for a PTH-induced specific phosphorylating substrate on their membrane microdomains by immunoblotting with specific antibody against phospho substrates of protein kinases [37].
 

Co-localisations of PTH

 

Regulatory relationships of PTH

 

Other interactions of PTH

 

Analytical, diagnostic and therapeutic context of PTH

References

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  4. Parathyroid hormone 7-84 induces hypocalcemia and inhibits the parathyroid hormone 1-84 secretory response to hypocalcemia in rats with intact parathyroid glands. Huan, J., Olgaard, K., Nielsen, L.B., Lewin, E. J. Am. Soc. Nephrol. (2006) [Pubmed]
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  17. Inhibition of renal adenylate cyclase by plasma from uremic patients. Jüppner, H., Hesch, R.D. J. Endocrinol. Invest. (1982) [Pubmed]
  18. Parathyroid hormone-related protein (PTHrP) does not regulate 1,25-dihydroxyvitamin D serum levels in hypercalcemia of malignancy. Schilling, T., Pecherstorfer, M., Blind, E., Leidig, G., Ziegler, R., Raue, F. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  19. Direct modulation by androgens of the response of human bone cells (SaOS-2) to human parathyroid hormone (PTH) and PTH-related protein. Fukayama, S., Tashjian, A.H. Endocrinology (1989) [Pubmed]
  20. Effects of a synthetic peptide of a parathyroid hormone-related protein on calcium homeostasis, renal tubular calcium reabsorption, and bone metabolism in vivo and in vitro in rodents. Yates, A.J., Gutierrez, G.E., Smolens, P., Travis, P.S., Katz, M.S., Aufdemorte, T.B., Boyce, B.F., Hymer, T.K., Poser, J.W., Mundy, G.R. J. Clin. Invest. (1988) [Pubmed]
  21. Parathyroid hormone controls receptor activator of NF-kappaB ligand gene expression via a distant transcriptional enhancer. Fu, Q., Manolagas, S.C., O'Brien, C.A. Mol. Cell. Biol. (2006) [Pubmed]
  22. Distinct beta-Arrestin- and G Protein-dependent Pathways for Parathyroid Hormone Receptor-stimulated ERK1/2 Activation. Gesty-Palmer, D., Chen, M., Reiter, E., Ahn, S., Nelson, C.D., Wang, S., Eckhardt, A.E., Cowan, C.L., Spurney, R.F., Luttrell, L.M., Lefkowitz, R.J. J. Biol. Chem. (2006) [Pubmed]
  23. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Suda, T., Takahashi, N., Udagawa, N., Jimi, E., Gillespie, M.T., Martin, T.J. Endocr. Rev. (1999) [Pubmed]
  24. Activation of receptor activator of NF-kappaB ligand gene expression by 1,25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. Kim, S., Yamazaki, M., Zella, L.A., Shevde, N.K., Pike, J.W. Mol. Cell. Biol. (2006) [Pubmed]
  25. Menin inactivation leads to loss of transforming growth factor beta inhibition of parathyroid cell proliferation and parathyroid hormone secretion. Sowa, H., Kaji, H., Kitazawa, R., Kitazawa, S., Tsukamoto, T., Yano, S., Tsukada, T., Canaff, L., Hendy, G.N., Sugimoto, T., Chihara, K. Cancer Res. (2004) [Pubmed]
  26. Nurse-like cells from patients with rheumatoid arthritis support the survival of osteoclast precursors via macrophage colony-stimulating factor production. Tsuboi, H., Udagawa, N., Hashimoto, J., Yoshikawa, H., Takahashi, N., Ochi, T. Arthritis Rheum. (2005) [Pubmed]
  27. Synthetic peptides comprising the amino-terminal sequence of a parathyroid hormone-like protein from human malignancies. Binding to parathyroid hormone receptors and activation of adenylate cyclase in bone cells and kidney. Nissenson, R.A., Diep, D., Strewler, G.J. J. Biol. Chem. (1988) [Pubmed]
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  29. Endogenous prostaglandin E2 and insulin-like growth factor 1 can modulate the levels of parathyroid hormone receptor in human osteoarthritic osteoblasts. Hilal, G., Massicotte, F., Martel-Pelletier, J., Fernandes, J.C., Pelletier, J.P., Lajeunesse, D. J. Bone Miner. Res. (2001) [Pubmed]
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  32. G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells. Offermanns, S., Iida-Klein, A., Segre, G.V., Simon, M.I. Mol. Endocrinol. (1996) [Pubmed]
  33. The receptor for parathyroid hormone and parathyroid hormone-related peptide is hydrolyzed and its signaling properties are altered by directly binding the calpain small subunit. Shimada, M., Mahon, M.J., Greer, P.A., Segre, G.V. Endocrinology (2005) [Pubmed]
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