parathyroid hormone related protein


Summary: A ubiquitously expressed, secreted protein with bone resorption and renal calcium reabsorption activities that are similar to PARATHYROID HORMONE. It does not circulate in appreciable amounts in normal subjects, but rather exerts its biological actions locally. Overexpression of parathyroid hormone-related protein by tumor cells results in humoral calcemia of malignancy.

Top Publications

  1. Torday J, Rehan V. Up-regulation of fetal rat lung parathyroid hormone-related protein gene regulatory network down-regulates the Sonic Hedgehog/Wnt/betacatenin gene regulatory network. Pediatr Res. 2006;60:382-8 pubmed
    ..This is the first evidence that alveolar fluid distension is an organizing principle for PTHrP signaling down-regulation of the Shh/Wnt/betacatenin pathway. ..
  2. Horwitz M, Tedesco M, Garcia Ocana A, Sereika S, Prebehala L, Bisello A, et al. Parathyroid hormone-related protein for the treatment of postmenopausal osteoporosis: defining the maximal tolerable dose. J Clin Endocrinol Metab. 2010;95:1279-87 pubmed publisher
    ..Unlike PTH, which is a mixed anabolic and catabolic agent, PTHrP displays features suggesting that it may be a pure anabolic agent when intermittently administered. The full dose range of PTHrP is unknown...
  3. DaSilva J, Gioeli D, Weber M, Parsons S. The neuroendocrine-derived peptide parathyroid hormone-related protein promotes prostate cancer cell growth by stabilizing the androgen receptor. Cancer Res. 2009;69:7402-11 pubmed publisher
    ..These events result in increased accumulation of AR and thus enhanced growth of prostate cancer cells at low levels of androgen. ..
  4. Müller M, Gagiannis S, Nawroth P, Brune M, Schilling T. Activation of the receptor for parathyroid hormone and parathyroid hormone related protein induces apoptosis via the extrinsic and intrinsic signaling pathway. Int J Mol Med. 2009;24:373-80 pubmed
    ..Thus, beyond its importance in development and differentiation, we describe an important role for the PTH/PTHrP receptor system in apoptosis of differentiating/embryonic cells. ..
  5. Mak K, Bi Y, Wan C, Chuang P, Clemens T, Young M, et al. Hedgehog signaling in mature osteoblasts regulates bone formation and resorption by controlling PTHrP and RANKL expression. Dev Cell. 2008;14:674-88 pubmed publisher
    ..Our results demonstrate that Hh signaling in mature osteoblasts regulates both bone formation and resorption and that inhibition of Hh signaling reduces bone loss in aged mice. ..
  6. Vasavada R, Wang L, Fujinaka Y, Takane K, Rosa T, Mellado Gil J, et al. Protein kinase C-zeta activation markedly enhances beta-cell proliferation: an essential role in growth factor mediated beta-cell mitogenesis. Diabetes. 2007;56:2732-43 pubmed
    ..PKC zeta is essential for PTHrP- and HGF-induced beta-cell proliferation. PKC zeta activation could be useful in therapeutic strategies for expanding beta-cell mass in vitro and in vivo. ..
  7. Nadella M, Dirksen W, Nadella K, Shu S, Cheng A, Morgenstern J, et al. Transcriptional regulation of parathyroid hormone-related protein promoter P2 by NF-kappaB in adult T-cell leukemia/lymphoma. Leukemia. 2007;21:1752-62 pubmed
    ..In summary, the data demonstrated that transcriptional regulation of PTHrP in ATLL cells can be controlled by NF-kappaB activation and also suggest a Tax-independent mechanism of activation of PTHrP in ATLL. ..
  8. Torday J, Rehan V. Developmental cell/molecular biologic approach to the etiology and treatment of bronchopulmonary dysplasia. Pediatr Res. 2007;62:2-7 pubmed
    ..It is critically important to judiciously select physiologically and developmentally relevant interventions when treating the preterm neonate. ..
  9. Datta N, Pettway G, Chen C, Koh A, McCauley L. Cyclin D1 as a target for the proliferative effects of PTH and PTHrP in early osteoblastic cells. J Bone Miner Res. 2007;22:951-64 pubmed
    ..These data indicate that PTH and PTHrP induce cyclin D1 expression in early osteoblastic cells and their action is developmental stage specific. ..

More Information


  1. Rehan V, Dargan Batra S, Wang Y, Cerny L, Sakurai R, Santos J, et al. A paradoxical temporal response of the PTHrP/PPARgamma signaling pathway to lipopolysaccharide in an in vitro model of the developing rat lung. Am J Physiol Lung Cell Mol Physiol. 2007;293:L182-90 pubmed
  2. Rehan V, Sakurai R, Wang Y, Santos J, Huynh K, Torday J. Reversal of nicotine-induced alveolar lipofibroblast-to-myofibroblast transdifferentiation by stimulants of parathyroid hormone-related protein signaling. Lung. 2007;185:151-9 pubmed
  3. Ng A, Yang Y, Wong R, Hägg E, Rabie A. Factors regulating condylar cartilage growth under repeated load application. Front Biosci. 2006;11:949-54 pubmed
    ..In conclusions, repeated mechanical loading on the condyle triggers the expression of PTHrP and SOX9, which in turn promotes condylar cartilage growth...
  4. Tfelt Hansen J, Yano S, John Macleod R, Smajilovic S, Chattopadhyay N, Brown E. High calcium activates the EGF receptor potentially through the calcium-sensing receptor in Leydig cancer cells. Growth Factors. 2005;23:117-23 pubmed
    ..In conclusion, the calcium activates the EGFR, possibly through the CaR, to regulate downstream signaling events and important biological functions in a model of HHM. ..
  5. Richard V, Nadella M, Green P, Lairmore M, Feuer G, Foley J, et al. Transcriptional regulation of parathyroid hormone-related protein promoter P3 by ETS-1 in adult T-cell leukemia/lymphoma. Leukemia. 2005;19:1175-83 pubmed
    ..Our data demonstrate that transcriptional regulation of PTHrP in ATLL cells can be controlled by T-cell receptor signaling and the ETS and MAPK ERK pathway in a Tax-independent manner. ..
  6. Fiaschi Taesch N, Stewart A. Minireview: parathyroid hormone-related protein as an intracrine factor--trafficking mechanisms and functional consequences. Endocrinology. 2003;144:407-11 pubmed
    ..This review discusses the mechanisms by which PTHrP may gain access to the nucleus/nucleolus and the functional consequences of this nuclear entry by PTHrP. ..
  7. Fujinaka Y, Sipula D, Garcia Ocana A, Vasavada R. Characterization of mice doubly transgenic for parathyroid hormone-related protein and murine placental lactogen: a novel role for placental lactogen in pancreatic beta-cell survival. Diabetes. 2004;53:3120-30 pubmed
    ..Placental lactogen 1 is an attractive target for future therapeutic strategies in diabetes. ..
  8. Yano S, Macleod R, Chattopadhyay N, Tfelt Hansen J, Kifor O, Butters R, et al. Calcium-sensing receptor activation stimulates parathyroid hormone-related protein secretion in prostate cancer cells: role of epidermal growth factor receptor transactivation. Bone. 2004;35:664-72 pubmed
    ..This transactivation is most likely mediated by activation of MMP and cleavage of proheparin-binding EGF (proHB-EGF) to HB-EGF. ..
  9. Tfelt Hansen J, Chattopadhyay N, Yano S, Kanuparthi D, Rooney P, Schwarz P, et al. Calcium-sensing receptor induces proliferation through p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase but not extracellularly regulated kinase in a model of humoral hypercalcemia of malignancy. Endocrinology. 2004;145:1211-7 pubmed
    ..These effects are likely direct without the involvement of PTHrP in an autocrine mode. ..
  10. Sato K, Onuma E, Yocum R, Ogata E. Treatment of malignancy-associated hypercalcemia and cachexia with humanized anti-parathyroid hormone-related protein antibody. Semin Oncol. 2003;30:167-73 pubmed
    ..These results suggest that the humanized antibody would be an effective and beneficial agent for patients with HHM, and that PTHrP is a major pathogenetic factor of hypercalcemia and cachexia in patients with HHM. ..
  11. Zhang B, Hosaka M, Sawada Y, Torii S, Mizutani S, Ogata M, et al. Parathyroid hormone-related protein induces insulin expression through activation of MAP kinase-specific phosphatase-1 that dephosphorylates c-Jun NH2-terminal kinase in pancreatic beta-cells. Diabetes. 2003;52:2720-30 pubmed
    ..The phosphorylated form of c-jun is known to repress cAMP-dependent insulin gene promoter activity. Thus, MKP-1 controls the insulin expression by downregulating a JNK/c-jun pathway. ..