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Gene Review

Pthlh  -  parathyroid hormone-like hormone

Rattus norvegicus

Synonyms: PLP, PTH-rP, PTHrP, Parathyroid hormone-like protein, Parathyroid hormone-related protein, ...
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Disease relevance of Pthlh


High impact information on Pthlh

  • These findings suggest that PTH-LP plays a physiological role in lactation, possibly as a hormone for the mobilization or transfer (or both) of calcium to the milk [1].
  • We found that expression of a GRK inhibitor enhanced parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor-stimulated cAMP generation and inhibited agonist-induced phosphorylation of this receptor in cell culture systems, consistent with attenuation of receptor desensitization [5].
  • We have examined the effects of 1,25 dihydroxyvitamin D3 (1,25[OH]2D3) and a low calcemic analogue EB1089 on parathyroid hormone-related peptide (PTHRP) production and on the development of hypercalcemia in Fischer rats implanted with the Leydig cell tumor H-500 [6].
  • In addition, PTHrP localized to glomerular epithelial cells (visceral and parietal), but not to mesangial cells [7].
  • The myelin proteolipid proteins (PLP and DM20) are believed to act as "adhesive struts" in the extracellular apposition of the CNS myelin sheath [8].

Chemical compound and disease context of Pthlh


Biological context of Pthlh

  • This is the first evidence that alveolar fluid distension is an organizing principle for PTHrP signaling down-regulation of the Shh/Wnt/betacatenin pathway [14].
  • RNase protection assay and real-time quantitative PCR analysis were used to assay PTHrP gene expression [15].
  • Parathyroid hormone-related protein (PTHrP) is a locally produced poly-protein that regulates cell growth [2].
  • To define the genetic elements important for the control of PTHrP gene transcription, we used the reverse transcription polymerase chain reaction to delineate the control of promoter utilization and the splicing patterns of the exons encoding 5'-untranslated sequences [16].
  • The results of these experiments provide evidence for cell- and tissue-specific utilization of 1) distinct human PTHrP transcription start sites and specific patterns of 5'-exon splicing and 2) multiple positive and negative DNA control elements, important for the regulation of human and rat PTHrP gene transcription [16].

Anatomical context of Pthlh


Associations of Pthlh with chemical compounds


Physical interactions of Pthlh


Regulatory relationships of Pthlh


Other interactions of Pthlh

  • During intramembranous ossification, PTHrP mRNA, IGF-I mRNA and IGF receptors were detected in preosteoblasts, differentiated osteoblasts and osteocytes in the newly formed trabecular bone [17].
  • Parathyroid hormone (PTH) regulates osteoblast function via a G protein-linked PTH/PTH-related protein (PTHrP) receptor [28].
  • Therefore, modulation of PTHrP gene transcription by 1,25-(OH)2D3 is mediated by the VDR interacting with one or both of the identified motifs in the 5'-flanking sequence of the gene [12].
  • Moreover, PTHrP mRNA overexpression by either FA or Ang II occurred in NRK 52E that were transfected with a CREB construct but not the dominant-negative CREB133 construct [29].
  • Regulation of RGS-2 may constitute a novel mechanism by which steroids modulate signaling via the PTH/PTHrP receptor and other G protein-coupled receptors in bone [30].

Analytical, diagnostic and therapeutic context of Pthlh


  1. Expression of a calcium-mobilizing parathyroid hormone-like peptide in lactating mammary tissue. Thiede, M.A., Rodan, G.A. Science (1988) [Pubmed]
  2. Role of parathyroid hormone-related protein in the regulation of stretch-induced renal vascular smooth muscle cell proliferation. Schordan, E., Welsch, S., Rothhut, S., Lambert, A., Barthelmebs, M., Helwig, J.J., Massfelder, T. J. Am. Soc. Nephrol. (2004) [Pubmed]
  3. Insulin-like growth factor I suppresses parathyroid hormone (PTH)/PTH-related protein receptor expression via a mitogen-activated protein kinase pathway in UMR-106 osteoblast-like cells. Kawane, T., Horiuchi, N. Endocrinology (1999) [Pubmed]
  4. Parathyroid hormone-related protein induction in focal stroke: a neuroprotective vascular peptide. Funk, J.L., Migliati, E., Chen, G., Wei, H., Wilson, J., Downey, K.J., Mullarky, P.J., Coull, B.M., McDonagh, P.F., Ritter, L.S. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2003) [Pubmed]
  5. Anabolic effects of a G protein-coupled receptor kinase inhibitor expressed in osteoblasts. Spurney, R.F., Flannery, P.J., Garner, S.C., Athirakul, K., Liu, S., Guilak, F., Quarles, L.D. J. Clin. Invest. (2002) [Pubmed]
  6. A vitamin D analogue (EB1089) inhibits parathyroid hormone-related peptide production and prevents the development of malignancy-associated hypercalcemia in vivo. Haq, M., Kremer, R., Goltzman, D., Rabbani, S.A. J. Clin. Invest. (1993) [Pubmed]
  7. Expression of parathyroid hormone-related protein in the rat glomerulus and tubule during recovery from renal ischemia. Soifer, N.E., Van Why, S.K., Ganz, M.B., Kashgarian, M., Siegel, N.J., Stewart, A.F. J. Clin. Invest. (1993) [Pubmed]
  8. A proteolipid protein gene family: expression in sharks and rays and possible evolution from an ancestral gene encoding a pore-forming polypeptide. Kitagawa, K., Sinoway, M.P., Yang, C., Gould, R.M., Colman, D.R. Neuron (1993) [Pubmed]
  9. 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]
  10. Vitamin B6 metabolism in liver and liver-derived tumors. Meisler, N.T., Nutter, L.M., Thanassi, J.W. Cancer Res. (1982) [Pubmed]
  11. Vitamin B6 metabolism in McA-RH7777 cells. Meisler, N.T., Thanassi, J.W. Cancer Res. (1988) [Pubmed]
  12. 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]
  13. Treatment of humoral hypercalcemia of malignancy in rats with inhibitors of carbonic anhydrase. Brown, G.M., Morris, C.A., Mitnick, M.A., Insogna, K.L. J. Bone Miner. Res. (1990) [Pubmed]
  14. Up-Regulation of Fetal Rat Lung Parathyroid Hormone-Related Protein Gene Regulatory Network Down-Regulates the Sonic Hedgehog/Wnt/{beta}catenin Gene Regulatory Network. Torday, J.S., Rehan, V.K. Pediatr. Res. (2006) [Pubmed]
  15. Stretch-induced PTH-related protein gene expression in osteoblasts. Chen, X., Macica, C.M., Ng, K.W., Broadus, A.E. J. Bone Miner. Res. (2005) [Pubmed]
  16. Regulation of parathyroid hormone-related peptide (PTHrP) gene transcription: cell- and tissue-specific promoter utilization mediated by multiple positive and negative cis-acting DNA elements. Campos, R.V., Wang, C., Drucker, D.J. Mol. Endocrinol. (1992) [Pubmed]
  17. Expression of parathyroid hormone-related peptide and insulin-like growth factor I during rat fracture healing. Okazaki, K., Jingushi, S., Ikenoue, T., Urabe, K., Sakai, H., Iwamoto, Y. J. Orthop. Res. (2003) [Pubmed]
  18. Calcium-sensing receptor stimulates PTHrP release by pathways dependent on PKC, p38 MAPK, JNK, and ERK1/2 in H-500 cells. Tfelt-Hansen, J., MacLeod, R.J., Chattopadhyay, N., Yano, S., Quinn, S., Ren, X., Terwilliger, E.F., Schwarz, P., Brown, E.M. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  19. Altered calbindin mRNA expression and calcium regulating hormones in rat diabetic pregnancy. Hamilton, K., Tein, M., Glazier, J., Mawer, E.B., Berry, J.L., Balment, R.J., Boyd, R.D., Garland, H.O., Sibley, C.P. J. Endocrinol. (2000) [Pubmed]
  20. Regulation of parathyroid hormone-like peptide in cultured normal human keratinocytes. Effect of growth factors and 1,25 dihydroxyvitamin D3 on gene expression and secretion. Kremer, R., Karaplis, A.C., Henderson, J., Gulliver, W., Banville, D., Hendy, G.N., Goltzman, D. J. Clin. Invest. (1991) [Pubmed]
  21. Down-regulation of the receptor for parathyroid hormone (PTH) and PTH-related peptide by transforming growth factor-beta in primary fetal rat osteoblasts. Jongen, J.W., Willemstein-Van Hove, E.C., Van der Meer, J.M., Bos, M.P., Jüppner, H., Segre, G.V., Abou-Samra, A.B., Feyen, J.H., Herrmann-Erlee, M.P. Endocrinology (1995) [Pubmed]
  22. Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin. Torday, J.S., Rehan, V.K. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  23. 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]
  24. 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]
  25. Antibody to beta3 integrin inhibits osteoclast-mediated bone resorption in the thyroparathyroidectomized rat. Crippes, B.A., Engleman, V.W., Settle, S.L., Delarco, J., Ornberg, R.L., Helfrich, M.H., Horton, M.A., Nickols, G.A. Endocrinology (1996) [Pubmed]
  26. Serum stimulation of parathyroid hormone-related peptide gene expression in ROS 17/2.8 osteosarcoma cells through transcriptional and posttranscriptional mechanisms. Falzon, M. Endocrinology (1996) [Pubmed]
  27. Tumor necrosis factor alpha inhibits the stimulatory effect of the parathyroid hormone-related protein on cyclic AMP formation in osteoblast-like cells via protein kinase C+. Blind, E., Knappe, V., Raue, F., Pfeilschifter, J., Ziegler, R. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  28. Parathyroid hormone (PTH) down-regulates PTH/PTH-related protein receptor gene expression in UMR-106 osteoblast-like cells via a 3',5'-cyclic adenosine monophosphate-dependent, protein kinase A-independent pathway. Kawane, T., Mimura, J., Yanagawa, T., Fujii-Kuriyama, Y., Horiuchi, N. J. Endocrinol. (2003) [Pubmed]
  29. Role of the renin-angiotensin system on the parathyroid hormone-related protein overexpression induced by nephrotoxic acute renal failure in the rat. Ortega, A., Rámila, D., Izquierdo, A., González, L., Barat, A., Gazapo, R., Bosch, R.J., Esbrit, P. J. Am. Soc. Nephrol. (2005) [Pubmed]
  30. Vitamin D and dexamethasone inversely regulate parathyroid hormone-induced regulator of G protein signaling-2 expression in osteoblast-like cells. Hömme, M., Schmitt, C.P., Himmele, R., Hoffmann, G.F., Mehls, O., Schaefer, F. Endocrinology (2003) [Pubmed]
  31. Characterization of PTH/PTHrP receptor in rat duodenum: effects of ageing. Gentili, C., Morelli, S., de Boland, A.R. J. Cell. Biochem. (2003) [Pubmed]
  32. Parathyroid hormone-like protein is a secretory product of atrial myocytes. Deftos, L.J., Burton, D.W., Brandt, D.W. J. Clin. Invest. (1993) [Pubmed]
  33. Intrauterine occupancy controls expression of the parathyroid hormone-related peptide gene in preterm rat myometrium. Thiede, M.A., Daifotis, A.G., Weir, E.C., Brines, M.L., Burtis, W.J., Ikeda, K., Dreyer, B.E., Garfield, R.E., Broadus, A.E. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
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