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Gene Review

PTH1R  -  parathyroid hormone 1 receptor

Homo sapiens

Synonyms: PFE, PTH/PTHr receptor, PTH/PTHrP type I receptor, PTH1 receptor, PTHR, ...
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Disease relevance of PTHR1


High impact information on PTHR1


Chemical compound and disease context of PTHR1


Biological context of PTHR1

  • Furthermore, we show that cells within the bone-perichondrial ring in controls and patients express IHH, PTHR1, and type 10 and type 1 collagen transcripts, suggesting that bone-perichondrial ring formation involves cells of both chondrocytic and osteoblastic phenotypes [13].
  • Using the program MapMaker/Sibs there was suggestive evidence of linkage between BMD and PTHR1 (maximum LOD score obtained [MLS] 2.7-3.5) [14].
  • Southern analysis of genomic DNA from lymphoblastoid cell lines of eight nonfamilial patients with PHP-1b revealed neither gross rearrangements nor methylation abnormalities in the P3 promoter region of the PTHR1 gene [15].
  • PTH1R1 signaling is required both in the adult and during development, and ablation of PTHR1 gene expression results in an embryonic lethal phenotype in both mice and humans [16].
  • With the advent of advances in chemical and molecular biology, the structure of PTH and its principal receptor (PTHrP-receptor [PTHR1]) were established [17].

Anatomical context of PTHR1


Associations of PTHR1 with chemical compounds


Physical interactions of PTHR1

  • Because heterologous desensitization can explain a decrease in PTH binding but cannot account for reduced PTH-R expression, we looked at the possible effect of insulin-like growth factor 1 (IGF-1) on this parameter [23].
  • Taken together, our studies suggest that the putative -45 to -39 MAZ-binding site regulates the constitutive activity of human PTHR1 P2 promoter [28].
  • Parathyroid hormone-related protein (PTHrP) regulates proliferation and differentiation of osteoblastic cells via binding to the parathyroid hormone receptor (PTH-1R) [29].
  • PTH-induced cAMP accumulation was similar in both cell lines suggesting that addition of the GFP to the cytoplasmic tail of the PTH receptor does not alter the ligand binding or G-protein coupling properties of the receptor [26].

Enzymatic interactions of PTHR1

  • 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 [30].
  • Thus, the agonist-occupied PTH receptor is phosphorylated by a kinase similar or identical to GRK2 in HEK-293 cells, but this phosphorylation is not requisite for efficient receptor endocytosis [30].

Regulatory relationships of PTHR1

  • CONCLUSION: These findings demonstrate that factors present in UUF decrease PTH-stimulated cAMP generation by a mechanism that involves a decrease in the levels of PTH1R mRNA levels [31].
  • Internalization determinants of the parathyroid hormone receptor differentially regulate beta-arrestin/receptor association [32].
  • In vessels of SHR, PTHrP was upregulated by 40% and type 1 PTH receptor (PTH1R) was downregulated by 65% compared with normotensive rats [33].

Other interactions of PTHR1


Analytical, diagnostic and therapeutic context of PTHR1


  1. A mutant PTH/PTHrP type I receptor in enchondromatosis. Hopyan, S., Gokgoz, N., Poon, R., Gensure, R.C., Yu, C., Cole, W.G., Bell, R.S., Jüppner, H., Andrulis, I.L., Wunder, J.S., Alman, B.A. Nat. Genet. (2002) [Pubmed]
  2. Absence of functional type 1 parathyroid hormone (PTH)/PTH-related protein receptors in humans is associated with abnormal breast development and tooth impaction. Wysolmerski, J.J., Cormier, S., Philbrick, W.M., Dann, P., Zhang, J.P., Roume, J., Delezoide, A.L., Silve, C. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  3. Absence of IHH and retention of PTHrP signalling in enchondromas and central chondrosarcomas. Rozeman, L.B., Hameetman, L., Cleton-Jansen, A.M., Taminiau, A.H., Hogendoorn, P.C., Bovée, J.V. J. Pathol. (2005) [Pubmed]
  4. Enchondromatosis (Ollier disease, Maffucci syndrome) is not caused by the PTHR1 mutation p.R150C. Rozeman, L.B., Sangiorgi, L., Briaire-de Bruijn, I.H., Mainil-Varlet, P., Bertoni, F., Cleton-Jansen, A.M., Hogendoorn, P.C., Bovée, J.V. Hum. Mutat. (2004) [Pubmed]
  5. The N-terminal fragment of human parathyroid hormone receptor 1 constitutes a hormone binding domain and reveals a distinct disulfide pattern. Grauschopf, U., Lilie, H., Honold, K., Wozny, M., Reusch, D., Esswein, A., Schäfer, W., Rücknagel, K.P., Rudolph, R. Biochemistry (2000) [Pubmed]
  6. A parathyroid hormone-like protein from cultured human keratinocytes. Merendino, J.J., Insogna, K.L., Milstone, L.M., Broadus, A.E., Stewart, A.F. Science (1986) [Pubmed]
  7. Altered activity of the nucleotide regulatory site in the parathyroid hormone-sensitive adenylate cyclase from the renal cortex of a patient with pseudohypoparathyroidism. Drezner, M.K., Burch, W.M. J. Clin. Invest. (1978) [Pubmed]
  8. Phosphorylation-independent inhibition of parathyroid hormone receptor signaling by G protein-coupled receptor kinases. Dicker, F., Quitterer, U., Winstel, R., Honold, K., Lohse, M.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. Molecular cloning of the gene encoding the mouse parathyroid hormone/parathyroid hormone-related peptide receptor. McCuaig, K.A., Clarke, J.C., White, J.H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  10. Evaluation of renal parathyroid hormone receptor function in myotonic dystrophy. Konagaya, Y., Konagaya, M., Mano, Y., Takayanagi, T., Tomita, A. J. Neurol. Sci. (1985) [Pubmed]
  11. Activation of the Ca2+ message system by parathyroid hormone is dependent on the cell cycle. Bizzarri, C., Civitelli, R. Endocrinology (1994) [Pubmed]
  12. Pamidronate corrects the down-regulation of the renal parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor mRNA in rats bearing Walker tumors. Yaghoobian, J., Morieux, C., Denne, M.A., Bouizar, Z., Ureña, P., de Vernejoul, M.C. Horm. Metab. Res. (1998) [Pubmed]
  13. Parathyroid hormone receptor type 1/Indian hedgehog expression is preserved in the growth plate of human fetuses affected with fibroblast growth factor receptor type 3 activating mutations. Cormier, S., Delezoide, A.L., Benoist-Lasselin, C., Legeai-Mallet, L., Bonaventure, J., Silve, C. Am. J. Pathol. (2002) [Pubmed]
  14. Suggestive linkage of the parathyroid receptor type 1 to osteoporosis. Duncan, E.L., Brown, M.A., Sinsheimer, J., Bell, J., Carr, A.J., Wordsworth, B.P., Wass, J.A. J. Bone Miner. Res. (1999) [Pubmed]
  15. Analysis of the P3 promoter of the human parathyroid hormone (PTH)/PTH-related peptide receptor gene in pseudohypoparathyroidism type 1b. Minagawa, M., Watanabe, T., Kohno, Y., Mochizuki, H., Hendy, G.N., Goltzman, D., White, J.H., Yasuda, T. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  16. Developmental and tissue-specific regulation of parathyroid hormone (PTH)/PTH-related peptide receptor gene expression. Goltzman, D., White, J.H. Crit. Rev. Eukaryot. Gene Expr. (2000) [Pubmed]
  17. Parathyroid hormone: past and present. Potts, J.T. J. Endocrinol. (2005) [Pubmed]
  18. The control of bone growth by parathyroid hormone, leptin, & statins. Whitfield, J.F., Morley, P., Willick, G.E. Crit. Rev. Eukaryot. Gene Expr. (2002) [Pubmed]
  19. Cellular mechanisms of renal osteodystrophy. Hoyland, J.A., Picton, M.L. Kidney Int. Suppl. (1999) [Pubmed]
  20. Parathyroid hormone, its fragments and their analogs for the treatment of osteoporosis. Whitfield, J.F., Morley, P., Willick, G.E. Treatments in endocrinology. (2002) [Pubmed]
  21. Functional expression and signaling properties of cloned human parathyroid hormone receptor in Xenopus oocytes. Evidence for a novel signaling pathway. Tong, Y., Zull, J., Yu, L. J. Biol. Chem. (1996) [Pubmed]
  22. Defective chondrocyte proliferation and differentiation in osteochondromas of MHE patients. Benoist-Lasselin, C., de Margerie, E., Gibbs, L., Cormier, S., Silve, C., Nicolas, G., LeMerrer, M., Mallet, J.F., Munnich, A., Bonaventure, J., Zylberberg, L., Legeai-Mallet, L. Bone (2006) [Pubmed]
  23. 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]
  24. 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]
  25. Histidine at position 5 is the specificity "switch" between two parathyroid hormone receptor subtypes. Behar, V., Nakamoto, C., Greenberg, Z., Bisello, A., Suva, L.J., Rosenblatt, M., Chorev, M. Endocrinology (1996) [Pubmed]
  26. Quantitative analysis of agonist-dependent parathyroid hormone receptor trafficking in whole cells using a functional green fluorescent protein conjugate. Conway, B.R., Minor, L.K., Xu, J.Z., D'Andrea, M.R., Ghosh, R.N., Demarest, K.T. J. Cell. Physiol. (2001) [Pubmed]
  27. Heparin-insensitive calcium release from intracellular stores triggered by the recombinant human parathyroid hormone receptor. Seuwen, K., Boddeke, H.G. Br. J. Pharmacol. (1995) [Pubmed]
  28. Functional importance of Myc-associated zinc finger protein for the human parathyroid hormone (PTH)/PTH-related peptide receptor-1 P2 promoter constitutive activity. Leroy, C., Manen, D., Rizzoli, R., Lombès, M., Silve, C. J. Mol. Endocrinol. (2004) [Pubmed]
  29. Impact of the mitogen-activated protein kinase pathway on parathyroid hormone-related protein actions in osteoblasts. Chen, C., Koh, A.J., Datta, N.S., Zhang, J., Keller, E.T., Xiao, G., Franceschi, R.T., D'Silva, N.J., McCauley, L.K. J. Biol. Chem. (2004) [Pubmed]
  30. Identification of phosphorylation sites in the G protein-coupled receptor for parathyroid hormone. Receptor phosphorylation is not required for agonist-induced internalization. Malecz, N., Bambino, T., Bencsik, M., Nissenson, R.A. Mol. Endocrinol. (1998) [Pubmed]
  31. Regulation of PTH1 receptor expression by uremic ultrafiltrate in UMR 106-01 osteoblast-like cells. Disthabanchong, S., Hassan, H., McConkey, C.L., Martin, K.J., Gonzalez, E.A. Kidney Int. (2004) [Pubmed]
  32. Internalization determinants of the parathyroid hormone receptor differentially regulate beta-arrestin/receptor association. Vilardaga, J.P., Krasel, C., Chauvin, S., Bambino, T., Lohse, M.J., Nissenson, R.A. J. Biol. Chem. (2002) [Pubmed]
  33. Type 1 parathyroid hormone receptor expression level modulates renal tone and plasma renin activity in spontaneously hypertensive rat. Massfelder, T., Taesch, N., Fritsch, S., Eichinger, A., Barthelmebs, M., Stewart, A.F., Helwig, J.J. J. Am. Soc. Nephrol. (2002) [Pubmed]
  34. Turn-on switch in parathyroid hormone receptor by a two-step parathyroid hormone binding mechanism. Castro, M., Nikolaev, V.O., Palm, D., Lohse, M.J., Vilardaga, J.P. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  35. Parathyroid hormone-related peptide (hPTHrP) and parathyroid hormone-related peptide receptor type 1 (PTHR1) expression in human thymus. Gessi, M., Monego, G., Lauriola, L., Maggiano, N., Ranelletti, F.O. J. Histochem. Cytochem. (2005) [Pubmed]
  36. Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes. Long, J.R., Zhao, L.J., Liu, P.Y., Lu, Y., Dvornyk, V., Shen, H., Liu, Y.J., Zhang, Y.Y., Xiong, D.H., Xiao, P., Deng, H.W. BMC Genet. (2004) [Pubmed]
  37. Expression of cartilage growth plate signalling molecules in chondroblastoma. Romeo, S., Bovée, J.V., Jadnanansing, N.A., Taminiau, A.H., Hogendoorn, P.C. J. Pathol. (2004) [Pubmed]
  38. Assignment of the parathyroid hormone/parathyroid hormone-related peptide receptor (PTHR1) to rabbit chromosome band 9p14-->p13 by fluorescence in situ hybridization. Martin-DeLeon, P.A., Piumi, F., Canaff, L., Rogel-Gaillard, C., Hendy, G.N. Cytogenet. Cell Genet. (2001) [Pubmed]
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