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Gene Review

Pth1r  -  parathyroid hormone 1 receptor

Mus musculus

Synonyms: PPR, PTH-related peptide receptor, PTH/PTHr receptor, PTH/PTHrP receptor, PTH/PTHrP type I receptor, ...
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Disease relevance of Pthr1


High impact information on Pthr1

  • Pthr1-null fetuses had plasma PTHrP levels 11-fold higher than those of their littermates [4].
  • Expression of chondrocyte differentiation markers such as collagen type II, collagen type X, Indian hedgehog and the PTH-PTHrP receptor was normal in ILK-deficient growth plates [5].
  • In the current study, we show that blocking PTHrP with antibodies or antagonizing the common parathyroid hormone (PTH)/PTHrP receptor, the PTH1 receptor, dramatically blunts the expansion of human CCRC in vitro by promoting cell death [6].
  • In the third model in which the PPR was disrupted in about 30% of columnar chondrocytes, Ihh action in the periarticular chondrocytes was upregulated because of ectopically differentiated hypertrophic chondrocytes that had lost PPR [7].
  • Activation-independent PTH1R endocytosis proceeds through a distinct arrestin-independent mechanism that is operative in cells lacking the adaptor protein Na/H exchange regulatory factor 1 (NHERF1) (ezrin-binding protein 50) [8].

Biological context of Pthr1

  • Multipotential mesenchymal cells (C3H10T1/2) transfected with normal or mutant PTH-1Rs and MC3T3-E1 osteoblastic cells were used to explore the roles of PTH, PTHrP, and the PTH-1R in cell viability relative to osteoblastic differentiation [9].
  • Overexpression of wild-type PTH-1R increased cell numbers and promoted osteocalcin gene expression versus inactivated mutant receptors [9].
  • PTH1R endocytosis was sensitive to protein kinase C inhibition [10].
  • Removal of most of the C terminus of the PTH1R eliminated receptor phosphorylation and the cAMP/protein kinase C sensitivity of internalization [10].
  • PTH(1-34) and (7-34) internalized the truncated PTH1R with identical kinetics, and the response was unaffected by forskolin [10].

Anatomical context of Pthr1

  • High-glucose (25 mm) medium was found to increase PTHrP and PTH1R in tubuloepithelial cells, mesangial cells and podocytes in vitro [11].
  • Moreover, the fetal skins of the PTHrP and PPR knockouts (KOs) had reciprocal increases in the length, diameter, and density of capillaries [12].
  • Acceleration of periarticular to columnar differentiation was also noted in this mouse, while most of periarticular chondrocytes retained PPR signaling [7].
  • These conditionally transformed, PTH1R(-/-) clonal osteoblastic cell lines should prove useful for studies of the regulation of osteoblast differentiation and function by both endogenous nonclassical species of PTH (or PTHrP) receptors and mutant signal-selective PTH1Rs [13].
  • The specific roles of these PTH1R signals, or of responses to other types of PTH receptors that may be expressed, in regulating osteoblast function are incompletely understood [13].

Associations of Pthr1 with chemical compounds


Regulatory relationships of Pthr1

  • We investigated whether substitution of the sterically hindered and helix-promoting amino acid alpha-aminoisobutyric acid (Aib) in N-terminal PTH oligopeptides would improve the capacity of the peptide to activate the P1R [14].

Other interactions of Pthr1

  • In developing organs, parathyroid hormone (PTH)/parathyroid hormone-related protein (PTHrP) receptor (PPR) signaling inhibits proliferation and differentiation of mesenchyme-derived cell types resulting in control of morphogenic events [12].
  • This study provides further evidence that in the developing growth plate, cell cycle exit and upregulation of Ihh and PPR mRNA expression are coupled [17].
  • Replacement of residues 1--31 of mCRFR1 with their PTH1R counterparts resulted in a chimeric receptor, PEC, which had normal CRFR1 functional properties [18].
  • Acting, at least in part, through the PTH-1 receptor, PTHrP profoundly influences chondrocytic and osteogenic cell biology [19].
  • In the present study we demonstrated that the type alpha1(II) collagen promoter Jansen transgene restored most of the bone abnormalities in PPR(-/-) mice, but did not prevent their perinatal lethality [20].

Analytical, diagnostic and therapeutic context of Pthr1


  1. Stimulatory G protein directly regulates hypertrophic differentiation of growth plate cartilage in vivo. Bastepe, M., Weinstein, L.S., Ogata, N., Kawaguchi, H., Jüppner, H., Kronenberg, H.M., Chung, U.I. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Role of parathyroid hormone-related peptide and Indian hedgehog in skeletal development. Jüppner, H. Pediatr. Nephrol. (2000) [Pubmed]
  3. Inhibition of in vitro bone resorption by a parathyroid hormone receptor antagonist in the canine adenocarcinoma model of humoral hypercalcemia of malignancy. Rosol, T.J., Capen, C.C. Endocrinology (1988) [Pubmed]
  4. Fetal parathyroids are not required to maintain placental calcium transport. Kovacs, C.S., Manley, N.R., Moseley, J.M., Martin, T.J., Kronenberg, H.M. J. Clin. Invest. (2001) [Pubmed]
  5. Reduced chondrocyte proliferation and chondrodysplasia in mice lacking the integrin-linked kinase in chondrocytes. Terpstra, L., Prud'homme, J., Arabian, A., Takeda, S., Karsenty, G., Dedhar, S., St-Arnaud, R. J. Cell Biol. (2003) [Pubmed]
  6. Parathyroid hormone-related protein is an essential growth factor for human clear cell renal carcinoma and a target for the von Hippel-Lindau tumor suppressor gene. Massfelder, T., Lang, H., Schordan, E., Lindner, V., Rothhut, S., Welsch, S., Simon-Assmann, P., Barthelmebs, M., Jacqmin, D., Helwig, J.J. Cancer Res. (2004) [Pubmed]
  7. PTHrP and Indian hedgehog control differentiation of growth plate chondrocytes at multiple steps. Kobayashi, T., Chung, U.I., Schipani, E., Starbuck, M., Karsenty, G., Katagiri, T., Goad, D.L., Lanske, B., Kronenberg, H.M. Development (2002) [Pubmed]
  8. Activation-independent parathyroid hormone receptor internalization is regulated by NHERF1 (EBP50). Sneddon, W.B., Syme, C.A., Bisello, A., Magyar, C.E., Rochdi, M.D., Parent, J.L., Weinman, E.J., Abou-Samra, A.B., Friedman, P.A. J. Biol. Chem. (2003) [Pubmed]
  9. Parathyroid hormone and parathyroid hormone-related protein exert both pro- and anti-apoptotic effects in mesenchymal cells. Chen, H.L., Demiralp, B., Schneider, A., Koh, A.J., Silve, C., Wang, C.Y., McCauley, L.K. J. Biol. Chem. (2002) [Pubmed]
  10. Ligand-selective dissociation of activation and internalization of the parathyroid hormone (PTH) receptor: conditional efficacy of PTH peptide fragments. Sneddon, W.B., Magyar, C.E., Willick, G.E., Syme, C.A., Galbiati, F., Bisello, A., Friedman, P.A. Endocrinology (2004) [Pubmed]
  11. The parathyroid hormone-related protein system and diabetic nephropathy outcome in streptozotocin-induced diabetes. Izquierdo, A., López-Luna, P., Ortega, A., Romero, M., Guitiérrez-Tarrés, M.A., Arribas, I., Alvarez, M.J., Esbrit, P., Bosch, R.J. Kidney Int. (2006) [Pubmed]
  12. Parathyroid hormone hormone-related protein and the PTH receptor regulate angiogenesis of the skin. Diamond, A.G., Gonterman, R.M., Anderson, A.L., Menon, K., Offutt, C.D., Weaver, C.H., Philbrick, W.M., Foley, J. J. Invest. Dermatol. (2006) [Pubmed]
  13. Conditionally immortalized murine osteoblasts lacking the type 1 PTH/PTHrP receptor. Divieti, P., Lanske, B., Kronenberg, H.M., Bringhurst, F.R. J. Bone Miner. Res. (1998) [Pubmed]
  14. Parathyroid hormone (PTH)-(1-14) and -(1-11) analogs conformationally constrained by alpha-aminoisobutyric acid mediate full agonist responses via the juxtamembrane region of the PTH-1 receptor. Shimizu, N., Guo, J., Gardella, T.J. J. Biol. Chem. (2001) [Pubmed]
  15. Obligate mitogen-activated protein kinase activation in parathyroid hormone stimulation of calcium transport but not calcium signaling. Sneddon, W.B., Liu, F., Gesek, F.A., Friedman, P.A. Endocrinology (2000) [Pubmed]
  16. Regulation of renal parathyroid hormone receptor expression by 1, 25-dihydroxyvitamin D3 and retinoic acid. Sneddon, W.B., Barry, E.L., Coutermarsh, B.A., Gesek, F.A., Liu, F., Friedman, P.A. Cell. Physiol. Biochem. (1998) [Pubmed]
  17. Localization of Indian hedgehog and PTH/PTHrP receptor expression in relation to chondrocyte proliferation during mouse bone development. MacLean, H.E., Kronenberg, H.M. Dev. Growth Differ. (2005) [Pubmed]
  18. Juxtamembrane region of the amino terminus of the corticotropin releasing factor receptor type 1 is important for ligand interaction. Assil, I.Q., Qi, L.J., Arai, M., Shomali, M., Abou-Samra, A.B. Biochemistry (2001) [Pubmed]
  19. Role of PTHrP and PTH-1 receptor in endochondral bone development. Karaplis, A.C., Deckelbaum, R.A. Front. Biosci. (1998) [Pubmed]
  20. Partial rescue of PTH/PTHrP receptor knockout mice by targeted expression of the Jansen transgene. Soegiarto, D.W., Kiachopoulos, S., Schipani, E., Jüppner, H., Erben, R.G., Lanske, B. Endocrinology (2001) [Pubmed]
  21. Type 1 parathyroid hormone receptor (PTH1R) nuclear trafficking: association of PTH1R with importin alpha1 and beta. Pickard, B.W., Hodsman, A.B., Fraher, L.J., Watson, P.H. Endocrinology (2006) [Pubmed]
  22. Calcium-sensing receptor regulation of PTH-inhibitable proximal tubule phosphate transport. Ba, J., Brown, D., Friedman, P.A. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  23. Human PTH-(7-84) inhibits bone resorption in vitro via actions independent of the type 1 PTH/PTHrP receptor. Divieti, P., John, M.R., Jüppner, H., Bringhurst, F.R. Endocrinology (2002) [Pubmed]
  24. Response of immortalized murine cementoblasts/periodontal ligament cells to parathyroid hormone and parathyroid hormone-related protein in vitro. Ouyang, H., McCauley, L.K., Berry, J.E., D'Errico, J.A., Strayhorn, C.L., Somerman, M.J. Arch. Oral Biol. (2000) [Pubmed]
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