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Gene Review

PTHLH  -  parathyroid hormone-like hormone

Gallus gallus

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Disease relevance of PTHLH


High impact information on PTHLH

  • A synthetic hybrid peptide was synthesized, [Ala29]PTH(28-48), in which alanine replaced glutamine at position 29, as in the PTH-rP molecule [5].
  • Parathyroid hormone (PTH) receptor bindings were examined in the membrane fraction of the calvaria and the kidney of the hen by the use of [125I]PTH-related protein (PTHrP) binding assays [6].
  • These findings underscore the importance of cellular Ca(2+) in GPC function and suggest that PTHrP action in the growth plate is at least partially regulated by changes in basal [Ca(2+)](i) [7].
  • Since EGTA mimicked the effect of parathyroid hormone-related peptide (PTHrP) on GPC maturation, we examined the effect of low [Ca(2+)](i) on PTHrP expression [7].
  • PTHrP expression was examined in chondrocytes isolated from 3- to 5-week-old chick long bones [8].

Biological context of PTHLH


Anatomical context of PTHLH

  • Furthermore, while cells from the epiphysis are considered the physiologic source of PTHrP, the relative expression of PTHrP in epiphyseal and growth plate chondrocytes has not been defined [8].
  • In the oviduct tissues of adult birds, PTHrP mRNA was detected in the isthmus (membrane-secreting) and shell gland (calcium-secreting) portions, but not in magnum (albumin secreting) tissue [12].
  • Immunoreactive PTHrP was localized to the serosal membrane as well as the smooth muscle layer of serosal arterioles, suggesting that PTHrP may modulate vascular smooth muscle activity [12].
  • In support of this hypothesis, synthetic chicken PTHrP (1-34)NH2 was found to relax the resting tension of isolated shell gland blood vessels in a dose-dependent manner [12].
  • We localized the cycle-associated fluctuations in PTHrP mRNA levels to the shell gland serosa and smooth muscle layer [12].

Associations of PTHLH with chemical compounds

  • The structure of chicken osteostatin or parathyroid hormone-related protein (PTHrP) (residues 107-139) containing an Ala/Thr substitution at the N-terminus was studied using two-dimensional proton NMR spectroscopy in an aqueous environment [13].
  • Although all fractionated cells responded to PTHrP in culture by increasing thymidine incorporation and cAMP production and decreasing alkaline phosphatase activity, the magnitude of response was greatest in the proliferative chondrocytes [9].
  • In TD, either induced by thiram or by genetic selection, normal levels of PTH/PTHrP receptor gene expression were observed up to 21 days post-hatch [3].
  • However, PKA activation with dibutyryl cAMP mimicked PTHrP and blockade of PTHrP stimulation of PKA with H-89 inhibited the regulatory action of the factor [10].
  • Mimicking the PTHrP stimulation either of PKC with 1-oleoyl 2-acetyl glycerol or of a Ca2+ pulse with 65 mM KCl did not lead to PTHrP-like effects on any of the four markers examined [10].

Regulatory relationships of PTHLH


Other interactions of PTHLH

  • These findings demonstrate that PTHrP is expressed in chondrocytes undergoing endochondral ossification, and show regulation, at least in part, by TGF-beta through Smad mediated signaling events [1].
  • Bone morphogenetic proteins are considered likely intermediates in PTHrP signaling [9].
  • These data demonstrate that although activation of PKC or Ca2+ signals is not required, the cylic AMP-dependent A kinase is required for PTHrP to regulate key hallmarks of GPC phenotype [10].
  • While TGF-beta strongly inhibited all Wnts, PTHrP did not inhibit either Wnt8c or Wnt9a and had lesser effects on the expression of the other Wnts [15].

Analytical, diagnostic and therapeutic context of PTHLH

  • The highest levels of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTHR-1), and Indian hedgehog (Ihh) expression were also found in the hypertrophic fractions B1 and B2 and not in the prehypertrophic fraction B3, as expected from in situ hybridization data on PTHR-1 expression in fetal rodent or chicken growth plates [16].
  • Following coculture the PTHrP mRNA levels increased in the epiphyseal cells while the expression of type X collagen and Indian hedgehog transcripts decreased in growth plate chondrocytes [8].
  • Immunohistochemistry of tissue sections showed that PTHrP protein was evident throughout the chick epiphysis [17].
  • The importance of calcium in mediating radiation damage to growth plate chondrocytes was further demonstrated by the finding that the addition of 4.0 mM EGTA (a calcium chelator) to the cell cultures before irradiation prevented the decrease in PTHrP mRNA levels [14].
  • PTHrP was detected by Western blotting as a band of 16,400 Da in extracts from hypertrophic chondrocytes, but not from proliferative cells [17].


  1. PTHrP expression in chick sternal chondrocytes is regulated by TGF-beta through Smad-mediated signaling. Pateder, D.B., Ferguson, C.M., Ionescu, A.M., Schwarz, E.M., Rosier, R.N., Puzas, J.E., O'Keefe, R.J. J. Cell. Physiol. (2001) [Pubmed]
  2. A parathyroid-related peptide induces transcaltachia (the rapid, hormonal stimulation of intestinal Ca2+ transport). Zhou, L.X., Nemere, I., Norman, A.W. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  3. Parathyroid receptor gene expression by epiphyseal growth plates in rickets and tibial dyschondroplasia. Ben-Bassat, S., Genina, O., Lavelin, I., Leach, R.M., Pines, M. Mol. Cell. Endocrinol. (1999) [Pubmed]
  4. Chondrocyte terminal differentiation, apoptosis, and type X collagen expression are downregulated by parathyroid hormone. Harrington, E.K., Lunsford, L.E., Svoboda, K.K. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology. (2004) [Pubmed]
  5. Parathyroid hormone-related protein antagonizes the action of parathyroid hormone on adult cardiomyocytes. Schlüter, K.D., Wingender, E., Tegge, W., Piper, H.M. J. Biol. Chem. (1996) [Pubmed]
  6. Changes in parathyroid hormone receptor binding affinity during egg laying: implications for calcium homeostasis in chicken. Yasuoka, T., Kawashima, M., Takahashi, T., Iwata, A., Oka, N., Tanaka, K. J. Bone Miner. Res. (1996) [Pubmed]
  7. Growth plate chondrocyte maturation is regulated by basal intracellular calcium. Zuscik, M.J., D'Souza, M., Ionescu, A.M., Gunter, K.K., Gunter, T.E., O'Keefe, R.J., Schwarz, E.M., Puzas, J.E., Rosier, R.N. Exp. Cell Res. (2002) [Pubmed]
  8. PTHrP expression in chondrocytes, regulation by TGF-beta, and interactions between epiphyseal and growth plate chondrocytes. Pateder, D.B., Rosier, R.N., Schwarz, E.M., Reynolds, P.R., Puzas, J.E., D'Souza, M., O'Keefe, R.J. Exp. Cell Res. (2000) [Pubmed]
  9. Regulation of chondrocyte terminal differentiation in the postembryonic growth plate: the role of the PTHrP-Indian hedgehog axis. Farquharson, C., Jefferies, D., Seawright, E., Houston, B. Endocrinology (2001) [Pubmed]
  10. Parathyroid hormone-related peptide regulation of chick tibial growth plate chondrocyte maturation requires protein kinase A. Zuscik, M.J., O'Keefe, R.J., Gunter, T.E., Puzas, J.E., Schwarz, E.M., Rosier, R.N. J. Orthop. Res. (2002) [Pubmed]
  11. Effects of parathyroid hormone-related peptide on chick growth plate chondrocytes. Loveys, L.S., Gelb, D., Hurwitz, S.R., Puzas, J.E., Rosier, R.N. J. Orthop. Res. (1993) [Pubmed]
  12. Expression of the parathyroid hormone-related protein gene in the avian oviduct: potential role as a local modulator of vascular smooth muscle tension and shell gland motility during the egg-laying cycle. Thiede, M.A., Harm, S.C., McKee, R.L., Grasser, W.A., Duong, L.T., Leach, R.M. Endocrinology (1991) [Pubmed]
  13. Structure study of osteostatin PTHrP[Thr107](107-139). Cuthbertson, R.M., Kemp, B.E., Barden, J.A. Biochim. Biophys. Acta (1999) [Pubmed]
  14. The role of autocrine growth factors in radiation damage to the epiphyseal growth plate. Pateder, D.B., Eliseev, R.A., O'Keefe, R.J., Schwarz, E.M., Okunieff, P., Constine, L.S., Puzas, J.E., Rosier, R.N. Radiat. Res. (2001) [Pubmed]
  15. Wnt-mediated regulation of chondrocyte maturation: modulation by TGF-beta. Dong, Y., Drissi, H., Chen, M., Chen, D., Zuscik, M.J., Schwarz, E.M., O'Keefe, R.J. J. Cell. Biochem. (2005) [Pubmed]
  16. Four distinct chondrocyte populations in the fetal bovine growth plate: highest expression levels of PTH/PTHrP receptor, Indian hedgehog, and MMP-13 in hypertrophic chondrocytes and their suppression by PTH (1-34) and PTHrP (1-40). Weisser, J., Riemer, S., Schmidl, M., Suva, L.J., Pöschl, E., Bräuer, R., von der Mark, K. Exp. Cell Res. (2002) [Pubmed]
  17. Parathyroid hormone-related peptide expression in the epiphyseal growth plate of the juvenile chicken: evidence for the origin of the parathyroid hormone-related peptide found in the epiphyseal growth plate. Medill, N.J., Praul, C.A., Ford, B.C., Leach, R.M. J. Cell. Biochem. (2001) [Pubmed]
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