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Gene Review

Pth  -  parathyroid hormone

Rattus norvegicus

Synonyms: PTH, PTH-(1-84), Parathyrin, Parathyroid hormone, Pth1, ...
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Disease relevance of Pth

  • These results suggest that osteitis fibrosa caused by advanced s-HPT can be successfully reversed by a control of PTH at an appropriate level through the improvement of PTG hyperplasia as induced by DI-OCT+IV-OCT [1].
  • Expression of the gene encoding PTH-related peptide (PTHrP), a protein that plays a primary role in the development of humoral hypercalcemia of malignancy, is down-regulated at the transcriptional level by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] [2].
  • DI-OCT may introduce simultaneous VDR and CaSR upregulations and the regression of hyperplastic PTG, and these effects may provide a strategy for strongly suppressing PTH levels in very severe secondary hyperparathyroidism [3].
  • The parathyroid hormone-induced bone resorption in mouse fetal long bone cultures was inhibited with an IC(50) of 16microg/ml [4].
  • Of considerable importance is that these analogs, given to rats at daily doses of up to 70 microg/kg of body weight per day, are either unable or only slightly able to raise serum calcium concentration but are nevertheless able to suppress parathyroid hormone levels in plasma up to 100% and induce 24-hydroxylase mRNA in skin [5].

Psychiatry related information on Pth


High impact information on Pth

  • The major ones, however, are the circulating amounts of parathyroid hormone (the secretion of which is stimulated by low serum calcium), serum or extracellular fluid phosphorus concentrations, circulating levels of 1,25(OH)2D3 itself, and perhaps serum calcium directly [11].
  • Parathyroid hormone-responsive adenylate cyclase in induced transplantable osteogenic rat sarcoma [12].
  • Parathyroid hormone as a smooth muscle relaxant [13].
  • Moreover, extracts from lactating mammary tissue stimulated parathyroid hormone-dependent adenylate cyclase [14].
  • When the analog and parathyroid hormone were infused simultaneously to rats at a molar ratio of 200 to 1, the analog inhibited the excretion of urinary phosphate and adenosine 3',5'-monophosphate [15].

Chemical compound and disease context of Pth


Biological context of Pth


Anatomical context of Pth


Associations of Pth with chemical compounds

  • Incubation for 2 and 4 h with forskolin, Bt2cAMP, PTHrP or prostaglandin E2 caused an increase in the level of VDR mRNA comparable to that caused by PTH [23].
  • Inhibition of transcription with actinomycin D (10 micrograms/ml) completely abolished the PTH-induced increase of VDR mRNA and inhibition of translation with cycloheximide (1 microgram/ml) resulted in superinduction of VDR mRNA [23].
  • Low extracellular calcium (Ca) stimulates parathyroid hormone (PTH) secretion and also increases the renal synthesis of calcitriol (CTR), which is known to decrease PTH production [27].
  • One of these motifs resembles the negative VDRE (nVDRE) from the PTH gene, which is also down-regulated by vitamin D3 [2].
  • Plasma urea, creatinine, total calcium, phosphorus, and PTH levels were measured [24].

Physical interactions of Pth


Regulatory relationships of Pth


Other interactions of Pth

  • After 24 h the VDR mRNA level in PTH-treated cells returned to control level [23].
  • On the other hand, PTH augmented TGF-beta-induced transcriptional activity [21].
  • This study investigated whether Rho proteins modulate the PKCalpha translocation and IL-6 promoter activity stimulated by PTH in UMR-106 cells [34].
  • To confirm the interaction between PTH1R and both importin alpha(1) and beta, the complex was purified from total cell protein of osteoblast-like cells using a PTH-linked affinity chromatography column [35].
  • METHODS: Inhibitory activity against in vitro bone resorption was examined by measuring the Ca2+ release from murine calvariae cultured for 6 days, which were treated with interleukin-1 (IL-1), IL-6, or parathyroid hormone [36].

Analytical, diagnostic and therapeutic context of Pth

  • PKCalpha and PKCbetaI are translocated after treatment with PTH in UMR-106 osteoblastic cells; however, the pathway leading to PKC isozyme translocation is not established [34].
  • The higher dose of 1,25-(OH)2D3, 6 ng, significantly decreased PTH from 52.7 +/- 10.2 pg/mL in the uremic control group to 25.7 +/- 6.7 pg/mL (P < 0.01) [37].
  • A rat tail animal model with computer modeling was used to examine bone response to loading and PTH [38].
  • The mRNA for this gene, determined by Northern blotting with a riboprobe for PTH mRNA, was of identical size to the parathyroidal PTH, but its abundance in brain was less than 0.01% of that expressed in the parathyroid glands [39].
  • Southern analysis of these PCR and rapid amplification of cDNA end cDNA fragments further indicated homology with PTH cDNA [39].


  1. Direct maxacalcitol injection into hyperplastic parathyroids improves skeletal changes in secondary hyperparathyroidism. Shiizaki, K., Hatamura, I., Negi, S., Sakaguchi, T., Saji, F., Kunimoto, K., Okamoto, M., Imazeki, I., Muragaki, Y., Akizawa, T. Kidney Int. (2006) [Pubmed]
  2. DNA sequences in the rat parathyroid hormone-related peptide gene responsible for 1,25-dihydroxyvitamin D3-mediated transcriptional repression. Falzon, M. Mol. Endocrinol. (1996) [Pubmed]
  3. Biochemical and cellular effects of direct maxacalcitol injection into parathyroid gland in uremic rats. Shiizaki, K., Negi, S., Hatamura, I., Sakaguchi, T., Saji, F., Kunimoto, K., Mizobuchi, M., Imazeki, I., Ooshima, A., Akizawa, T. J. Am. Soc. Nephrol. (2005) [Pubmed]
  4. Herbal formulation, Yukmi-jihang-tang-Jahage, regulates bone resorption by inhibition of phosphorylation mediated by tyrosine kinase Src and cyclooxygenase expression. Jin, U.H., Kim, D.I., Lee, T.K., Lee, D.N., Kim, J.K., Lee, I.S., Kim, C.H. Journal of ethnopharmacology. (2006) [Pubmed]
  5. Biologically active noncalcemic analogs of 1alpha,25-dihydroxyvitamin D with an abbreviated side chain containing no hydroxyl. Plum, L.A., Prahl, J.M., Ma, X., Sicinski, R.R., Gowlugari, S., Clagett-Dame, M., DeLuca, H.F. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  6. Lithium inhibition of bone mineralization and osteoid formation. Baran, D.T., Schwartz, M.P., Bergfeld, M.A., Teitelbaum, S.L., Slatopolsky, E., Avioli, L.V. J. Clin. Invest. (1978) [Pubmed]
  7. Adverse effects of an active fragment of parathyroid hormone on rat hippocampal organotypic cultures. Hirasawa, T., Nakamura, T., Mizushima, A., Morita, M., Ezawa, I., Miyakawa, H., Kudo, Y. Br. J. Pharmacol. (2000) [Pubmed]
  8. Hyperalgesic activity of parathyroid hormone and its fragments in male rats. Clementi, G., Amico-Roxas, M., Nicoletti, F., Fiore, E.C., Prato, A., Scapagnini, U. Brain Res. (1984) [Pubmed]
  9. Effects of parathyroid hormone on bone formation in a rat model for chronic alcohol abuse. Turner, R.T., Evans, G.L., Zhang, M., Sibonga, J.D. Alcohol. Clin. Exp. Res. (2001) [Pubmed]
  10. Effect of prenatal ethanol exposure on fetal calcium metabolism. Keiver, K., Ellis, L., Anzarut, A., Weinberg, J. Alcohol. Clin. Exp. Res. (1997) [Pubmed]
  11. Metabolism of 1,25-dihydroxyvitamin D3. Kumar, R. Physiol. Rev. (1984) [Pubmed]
  12. Parathyroid hormone-responsive adenylate cyclase in induced transplantable osteogenic rat sarcoma. Martin, T.J., Ingleton, P.M., Underwood, J.C., Michelangeli, V.P., Hunt, N.H., Melick, R.A. Nature (1976) [Pubmed]
  13. Parathyroid hormone as a smooth muscle relaxant. Mok, L.L., Nickols, G.A., Thompson, J.C., Cooper, C.W. Endocr. Rev. (1989) [Pubmed]
  14. Expression of a calcium-mobilizing parathyroid hormone-like peptide in lactating mammary tissue. Thiede, M.A., Rodan, G.A. Science (1988) [Pubmed]
  15. A parathyroid hormone inhibitor in vivo: design and biological evaluation of a hormone analog. Horiuchi, N., Holick, M.F., Potts, J.T., Rosenblatt, M. Science (1983) [Pubmed]
  16. Effects of 19-nor-1,25(OH)2D2, a new analogue of calcitriol, on secondary hyperparathyroidism in uremic rats. Slatopolsky, E., Finch, J., Ritter, C., Takahashi, F. Am. J. Kidney Dis. (1998) [Pubmed]
  17. Mutual up-regulation of thyroid hormone and parathyroid hormone receptors in rat osteoblastic osteosarcoma 17/2.8 cells. Gu, W.X., Stern, P.H., Madison, L.D., Du, G.G. Endocrinology (2001) [Pubmed]
  18. The role of dietary calcium in the physiology of vitamin D toxicity: excess dietary vitamin D3 blunts parathyroid hormone induction of kidney 1-hydroxylase. Beckman, M.J., Johnson, J.A., Goff, J.P., Reinhardt, T.A., Beitz, D.C., Horst, R.L. Arch. Biochem. Biophys. (1995) [Pubmed]
  19. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats. Gowen, M., Stroup, G.B., Dodds, R.A., James, I.E., Votta, B.J., Smith, B.R., Bhatnagar, P.K., Lago, A.M., Callahan, J.F., DelMar, E.G., Miller, M.A., Nemeth, E.F., Fox, J. J. Clin. Invest. (2000) [Pubmed]
  20. DNA synthesis is not necessary for osteoclastic responses to parathyroid hormone in cultured fetal rat long bones. Lorenzo, J.A., Raisz, L.G., Hock, J.M. J. Clin. Invest. (1983) [Pubmed]
  21. Parathyroid hormone-Smad3 axis exerts anti-apoptotic action and augments anabolic action of transforming growth factor beta in osteoblasts. Sowa, H., Kaji, H., Iu, M.F., Tsukamoto, T., Sugimoto, T., Chihara, K. J. Biol. Chem. (2003) [Pubmed]
  22. Parathyroid hormone prevents 1,25 (OH)2D3 induced down-regulation of the vitamin D receptor in growth plate chondrocytes in vitro. Klaus, G., May, T., Hügel, U., von Eichel, B., Rodriguez, J., Fernandez, P., Reichrath, J., Ritz, E., Mehls, O. Kidney Int. (1997) [Pubmed]
  23. Regulation of 1,25-dihydroxyvitamin D3 receptor gene expression by parathyroid hormone and cAMP-agonists. van Leeuwen, J.P., Birkenhäger, J.C., Vink-van Wijngaarden, T., van den Bemd, G.J., Pols, H.A. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  24. Persistent downregulation of calcium-sensing receptor mRNA in rat parathyroids when severe secondary hyperparathyroidism is reversed by an isogenic kidney transplantation. Lewin, E., Garfia, B., Recio, F.L., Rodriguez, M., Olgaard, K. J. Am. Soc. Nephrol. (2002) [Pubmed]
  25. Evidence for coordinated regulation of osteoblast function by 1,25-dihydroxyvitamin D3 and parathyroid hormone. van Leeuwen, J.P., Birkenhäger, J.C., van den Bemd, G.C., Pols, H.A. Biochim. Biophys. Acta (1996) [Pubmed]
  26. Parathyroid hormone rapidly stimulates hyaluronan synthesis by periosteal osteoblasts in the tibial diaphysis of the growing rat. Midura, R.J., Su, X., Morcuende, J.A., Tammi, M., Tammi, R. J. Biol. Chem. (2003) [Pubmed]
  27. Regulation of parathyroid vitamin D receptor expression by extracellular calcium. Garfia, B., Cañadillas, S., Canalejo, A., Luque, F., Siendones, E., Quesada, M., Almadén, Y., Aguilera-Tejero, E., Rodríguez, M. J. Am. Soc. Nephrol. (2002) [Pubmed]
  28. Regulation of intestinal vitamin D receptor expression in experimental uraemia: effects of parathyroidectomy and administration of PTH. Szabó, A., Schmutz, A., Pesian, S., Schmidt-Gayk, H., Ritz, E., Reichel, H. Nephrol. Dial. Transplant. (1998) [Pubmed]
  29. Calreticulin inhibits vitamin D's action on the PTH gene in vitro and may prevent vitamin D's effect in vivo in hypocalcemic rats. Sela-Brown, A., Russell, J., Koszewski, N.J., Michalak, M., Naveh-Many, T., Silver, J. Mol. Endocrinol. (1998) [Pubmed]
  30. Parathyroid hormone (PTH) suppresses rat PTH/PTH-related protein receptor gene promoter. Kawane, T., Mimura, J., Fujii-Kuriyama, Y., Horiuchi, N. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  31. Starvation-induced increase in the parathyroid hormone/PTH-related protein receptor mRNA of bone and kidney in sham-operated and thyroparathyroidectomized rats. Kawane, T., Saikatsu, S., Akeno, N., Abe, M., Horiuchi, N. Eur. J. Endocrinol. (1997) [Pubmed]
  32. Transforming growth factor-beta1 regulates steady-state PTH/PTHrP receptor mRNA levels and PTHrP binding in ROS 17/2.8 osteosarcoma cells. McCauley, L.K., Beecher, C.A., Melton, M.E., Werkmeister, J.R., Jüppner, H., Abou-Samra, A.B., Segre, G.V., Rosol, T.J. Mol. Cell. Endocrinol. (1994) [Pubmed]
  33. Abnormal renovascular parathyroid hormone-1 receptor in hypertension: Primary defect or secondary to angiotensin ii type 1 receptor activation? Welsch, S., Schordan, E., Coquard, C., Massfelder, T., Fiaschi-Taesch, N., Helwig, J.J., Barthelmebs, M. Endocrinology (2006) [Pubmed]
  34. Rho and Rho kinase are involved in parathyroid hormone-stimulated protein kinase C alpha translocation and IL-6 promoter activity in osteoblastic cells. Radeff, J.M., Nagy, Z., Stern, P.H. J. Bone Miner. Res. (2004) [Pubmed]
  35. 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]
  36. Comparative analysis of the effects of a novel vacuolar adenosine 5'-triphosphatase inhibitor, FR202126, and doxycycline on bone loss caused by experimental periodontitis in rats. Niikura, K. J. Periodontol. (2006) [Pubmed]
  37. A new analog of 1,25-(OH)2D3, 19-NOR-1,25-(OH)2D2, suppresses serum PTH and parathyroid gland growth in uremic rats without elevation of intestinal vitamin D receptor content. Takahashi, F., Finch, J.L., Denda, M., Dusso, A.S., Brown, A.J., Slatopolsky, E. Am. J. Kidney Dis. (1997) [Pubmed]
  38. Trabecular bone response to mechanical and parathyroid hormone stimulation: the role of mechanical microenvironment. Kim, C.H., Takai, E., Zhou, H., von Stechow, D., Müller, R., Dempster, D.W., Guo, X.E. J. Bone Miner. Res. (2003) [Pubmed]
  39. Sequence analysis of hypothalamic parathyroid hormone messenger ribonucleic acid. Nutley, M.T., Parimi, S.A., Harvey, S. Endocrinology (1995) [Pubmed]
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