The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PTRH1  -  peptidyl-tRNA hydrolase 1 homolog (S....

Homo sapiens

Synonyms: C9orf115, PTH, PTH1
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of PTRH1

  • These animals developed levels of hPTH greater than 1.0 microgram/liter and became hypercalcemia within 20 days [1].
  • All other animals were injected with one of the hPTH analogs or hPTH(1-34) at 0, 4, 40, or 400 mu g/kg of body weight (BW)/day and were killed on day 84 [2].
  • cDNA encoding human preproPTH (hpreproPTH) was expressed in Escherichia coli to study the processing of the precursor to hPTH and its secretion by the bacterial secretory apparatus [3].
  • Thyroparathyroidectomy in these hypercalcemic rats producing hPTH did not result in hypocalcemia and tetany, which was observed in control animals undergoing thyroparathyroidectomy [4].
  • Recombinant retroviruses were used to transduce a functional hPTH gene into cultured rat fibroblasts [4].

High impact information on PTRH1

  • PTH-related peptide, probably also through PTH1 receptors, regulates skeletal, pancreatic, epidermal, and mammary gland differentiation and bladder and vascular smooth muscle relaxation and has a CNS role that is under investigation [5].
  • PTH regulates calcium homeostasis through bone and kidney PTH1 receptors [5].
  • PTHrP transcript was increased in SHR-derived cells whereas PTH1 receptor (PTH1R) transcripts were similar in both cell lines [6].
  • The structural characterization of TIP39 also provides some insight into the lack of affinity of this novel ligand for the PTH1 receptor [7].
  • Analysis of the structure-activity relationships in these tethered receptor constructs can provide new information concerning how the N-terminal residues of PTH interact with the extracellular loops and transmembrane regions of the PTH-1 receptor, particularly in regard to receptor activation [8].

Chemical compound and disease context of PTRH1

  • Chronic hPTH administration accelerated the development of hypertension and increased the pressor response to norepinephrine in rats fed a high calcium diet, but did not affect either parameter in rats fed a standard calcium diet [9].

Biological context of PTRH1

  • Understanding of the mechanisms regulating PTH1-Rc gene expression, receptor desensitization, endocytosis, recycling, and intracellular signaling is advancing and provides insights to understand PTH1-Rc's role in both normal and pathophysiology [10].
  • Taken together, these results demonstrate that the amino-terminal portion of PTH(1-34) interacts with the juxtamembrane regions of the PTH-1 receptor and that these interactions are sufficient for initiating signal transduction [11].
  • After accounting for the animal weight there was a further significant decrease in bone mineral content and density (BMC and BMD) on day 29 attributable to hPTH-mediated bone loss [1].
  • Since hPTH 1-34 may inhibit osteogenesis in Friedenstein chambers, it is possible that the increased osteoblastic activity induced by the daily injection regime in trabecular bone is dependent on the noncontinuous nature of the PTH stimulus [12].
  • Point mutations in the hPTH Sp1 element revealed the factor recognized a CAAT-like sequence resulting from a single nucleotide difference unique to the human sequence relative to other mammalian promoters [13].

Anatomical context of PTRH1

  • Both point-mutated hybrids, [Ile5]PTH-(1-34) and [His5]PTH-(1-34), bind to and stimulate cAMP accumulation and the release of cytosolic free calcium in HEK293/C-21, a clonal human embryonic kidney cell line stably expressing the recombinant hPTH/PTHrP receptor [14].
  • We randomly mutated codons 1-4 of human PTH (hPTH) with degenerate oligonucleotides and, after expression in COS cells, screened the mutants for receptor binding and cAMP-stimulating activity using ROS 17/2.8 cells [15].
  • Groups 1 and 2 receive the hPTH-secreting fibroblasts; group 2 subsequently received pamidronate (2.5 mg/kg IV) 18 and 27 days after receiving the fibroblasts [1].
  • The trypsin accessibility of hpreproPTH and of the two hPTH fragments in pulse-chase, cell-fractionation experiments using intact and lysed spheroplasts lets us conclude that the mammalian signal sequence directs hpreproPTH to the surface of the spheroplast membrane but is not appropriately cleaved by the signal peptidase [3].
  • CONTEXT: Although serum calcium (Ca2+) concentration regulates the generation of amino-terminally (N-terminally) truncated forms of human PTH (hPTH) degraded from (1-84)hPTH, no studies have yet reported whether the parathyroid gland itself is responsible for this process [16].

Associations of PTRH1 with chemical compounds

  • We conclude that intact methionine residues at positions 8 and 18 of hPTH 1-34 are necessary for all its major biological actions, including its effect on the renal metabolism of 25-hydroxyvitamin D3(25(OH)D3) [17].
  • Further, we examined the effect of the administration of pamidronate on bone mass and density in the presence of extremely high concentrations of hPTH [1].
  • Basal calcitriol levels rose from 115 +/- 17 to 163 +/- 16 pM (P = 0.0002), but the increase in calcitriol following hPTH infusion was unaffected by short-term rhGH [18].
  • Furthermore, we have found arginine 186 to be of critical importance to the interaction of the hPTH1 Rc with 125I-K13: modification of Arg186 to either lysine or alanine does not modify receptor avidity or signal transduction by the receptor, but eliminates cross-linking to 125I-K13 [19].
  • The ampouled hPTH was calibrated by immunoassays against the Research Standard of hPTH for immunoassay (ampoule code 75/549) distributed internationally from the National Institute for Biological Standards and Control since 1977 [20].

Physical interactions of PTRH1

  • This method is useful for measurement of agonist and antagonist radioligand binding at the PTH-1 receptor and binding of [125I]PTH(1-34) at the PTH-2 receptor [21].

Regulatory relationships of PTRH1

  • Previous studies on parathyroid hormone (PTH)(1-14) revealed that residues (1-9) played a dominant role in stimulating PTH-1 receptor-mediated increases in cAMP formation [22].

Other interactions of PTRH1

  • In particular, the [Bpa2]- and [Bpa4]-substituted analogs selectively antagonized and preferentially cross-linked to the PTH-1 receptor and PTH-2 receptor, respectively [23].
  • These results demonstrate that the 1-5 region of [I5,W23]-PTHrP(1-36) is critical for activating the PTH-1 and PTH-2 receptors and suggest that the individual residues in this region play distinct roles in modulating the activation states of the two receptors [23].
  • We investigated how the amino-terminal signaling portion of PTH interacts with the receptor by utilizing analogs of the weakly active fragment, rat (r) PTH(1-14)NH(2), and cells transfected with the wild-type human PTH-1 receptor (hP1R-WT) or a truncated PTH-1 receptor which lacked most of the amino-terminal extracellular domain (hP1R-delNt) [24].
  • The overall results thus reveal that two different types of inverse agonists are possible for PTHrP ligands (nonselective and selective) and that constitutively active PTH-1 receptors can access different conformational states [25].

Analytical, diagnostic and therapeutic context of PTRH1

  • Six patients with osteoporosis underwent detailed studies including blood and urinary measurements of calcium, phosphate, and magnesium; 47Ca kinetic studies; and 18-d balance studies before and during the short-term administration (3--4 wk) of a daily subcutaneous injection of hPTH fragment 1--34 given as 450 or 750 U/dose [26].
  • We conducted a 12-mo, randomized clinical trial of human parathyroid hormone 1-34 (hPTH 1-34) in postmenopausal women (mean age was 63 yr) with osteoporosis who were taking corticosteroids and hormone replacement therapy [27].
  • Biomechanics showed that ovariectomy weakened proximal femora compared with sham, but PTH1, PTH5, and PTH1W were stronger than OVX and not different from sham [28].
  • We evaluated spinal and femoral bone mass and density utilizing dual-energy x-ray absorptiometry (DEXA) in rats in which severe hyperparathyroidism was produced by the expression of the gene for human PTH-(1-84) (hPTH) [1].
  • A direct immunoassay for circulating intact human PTH (hPTH) is described [29].


  1. Pamidronate reduces PTH-mediated bone loss in a gene transfer model of hyperparathyroidism in rats. Mitlak, B.H., Rodda, C.P., Von Deck, M.D., Dobrolet, N.C., Neer, R.M., Nussbaum, S.R. J. Bone Miner. Res. (1991) [Pubmed]
  2. Bone-selective analogs of human PTH(1-34) increase bone formation in an ovariectomized rat model. Lane, N.E., Kimmel, D.B., Nilsson, M.H., Cohen, F.E., Newton, S., Nissenson, R.A., Strewler, G.J. J. Bone Miner. Res. (1996) [Pubmed]
  3. Human preproparathyroid hormone synthesized in Escherichia coli is transported to the surface of the bacterial inner membrane but not processed to the mature hormone. Born, W., Freeman, M., Hendy, G.N., Rapoport, A., Rich, A., Potts, J.T., Kronenberg, H.M. Mol. Endocrinol. (1987) [Pubmed]
  4. Somatic gene transfer in the development of an animal model for primary hyperparathyroidism. Wilson, J.M., Grossman, M., Thompson, A.R., Lupassikis, C., Rosenberg, A., Potts, J.T., Kronenberg, H.M., Mulligan, R.C., Nussbaum, S.R. Endocrinology (1992) [Pubmed]
  5. New members of the parathyroid hormone/parathyroid hormone receptor family: the parathyroid hormone 2 receptor and tuberoinfundibular peptide of 39 residues. Usdin, T.B., Wang, T., Hoare, S.R., Mezey, E., Palkovits, M. Frontiers in neuroendocrinology. (2000) [Pubmed]
  6. Paradoxical actions of exogenous and endogenous parathyroid hormone-related protein on renal vascular smooth muscle cell proliferation: reversion in the SHR model of genetic hypertension. Massfelder, T., Taesch, N., Endlich, N., Eichinger, A., Escande, B., Endlich, K., Barthelmebs, M., Helwig, J.J. FASEB J. (2001) [Pubmed]
  7. Structure of tuberoinfundibular peptide of 39 residues. Piserchio, A., Usdin, T., Mierke, D.F. J. Biol. Chem. (2000) [Pubmed]
  8. Autoactivation of type-1 parathyroid hormone receptors containing a tethered ligand. Shimizu, M., Carter, P.H., Gardella, T.J. J. Biol. Chem. (2000) [Pubmed]
  9. Chronic parathyroid hormone administration reverses the antihypertensive effect of calcium loading in young spontaneously hypertensive rats. Kishimoto, H., Tsumura, K., Fujioka, S., Uchimoto, S., Morii, H. Am. J. Hypertens. (1993) [Pubmed]
  10. Parathyroid hormone 1 receptor: insights into structure and function. Chorev, M. Recept. Channels (2002) [Pubmed]
  11. The (1-14) fragment of parathyroid hormone (PTH) activates intact and amino-terminally truncated PTH-1 receptors. Luck, M.D., Carter, P.H., Gardella, T.J. Mol. Endocrinol. (1999) [Pubmed]
  12. Effects of two treatment regimes with synthetic human parathyroid hormone fragment on bone formation and the tissue balance of trabecular bone in greyhounds. Podbesek, R., Edouard, C., Meunier, P.J., Parsons, J.A., Reeve, J., Stevenson, R.W., Zanelli, J.M. Endocrinology (1983) [Pubmed]
  13. Contrasting mammalian parathyroid hormone (PTH) promoters: nuclear factor-Y binds to a deoxyribonucleic acid element unique to the human PTH promoter and acts as a transcriptional enhancer. Alimov, A.P., Langub, M.C., Malluche, H.H., Park-Sarge, O.K., Koszewski, N.J. Endocrinology (2004) [Pubmed]
  14. Histidine at position 5 is the specificity "switch" between two parathyroid hormone receptor subtypes. Behar, V., Nakamoto, C., Greenberg, Z., Bisello, A., Suva, L.J., Rosenblatt, M., Chorev, M. Endocrinology (1996) [Pubmed]
  15. Mutational analysis of the receptor-activating region of human parathyroid hormone. Gardella, T.J., Axelrod, D., Rubin, D., Keutmann, H.T., Potts, J.T., Kronenberg, H.M., Nussbaum, S.R. J. Biol. Chem. (1991) [Pubmed]
  16. Direct in vitro evidence of extracellular Ca2+-induced amino-terminal truncation of human parathyroid hormone (1-84) by human parathyroid cells. Kawata, T., Imanishi, Y., Kobayashi, K., Onoda, N., Takemoto, Y., Tahara, H., Okuno, S., Ishimura, E., Miki, T., Ishikawa, T., Inaba, M., Nishizawa, Y. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  17. Effects of oxidation of human parathyroid hormone on its biological activity in continuously infused, thyroparathyroidectomized rats. Horiuchi, N. J. Bone Miner. Res. (1988) [Pubmed]
  18. Interactions of growth hormone and parathyroid hormone in renal phosphate, calcium, and calcitriol metabolism and bone remodeling in postmenopausal women. Lieberman, S.A., Holloway, L., Marcus, R., Hoffman, A.R. J. Bone Miner. Res. (1994) [Pubmed]
  19. Arginine 186 in the extracellular N-terminal region of the human parathyroid hormone 1 receptor is essential for contact with position 13 of the hormone. Adams, A.E., Bisello, A., Chorev, M., Rosenblatt, M., Suva, L.J. Mol. Endocrinol. (1998) [Pubmed]
  20. The first international reference preparation of human parathyroid hormone for immunoassay: characterization and calibration by international collaborative study. Zanelli, J.M., Gaines-Das, R.E. J. Clin. Endocrinol. Metab. (1983) [Pubmed]
  21. Quantitative cell membrane-based radioligand binding assays for parathyroid hormone receptors. Hoare, S.R., Usdin, T.B. Journal of pharmacological and toxicological methods. (1999) [Pubmed]
  22. Zinc(II)-mediated enhancement of the agonist activity of histidine-substituted parathyroid hormone(1-14) analogues. Carter, P.H., Gardella, T.J. Biochim. Biophys. Acta (2001) [Pubmed]
  23. Studies of the N-terminal region of a parathyroid hormone-related peptide (1-36) analog: receptor subtype-selective agonists, antagonists, and photochemical cross-linking agents. Carter, P.H., Jüppner, H., Gardella, T.J. Endocrinology (1999) [Pubmed]
  24. Minimization of parathyroid hormone. Novel amino-terminal parathyroid hormone fragments with enhanced potency in activating the type-1 parathyroid hormone receptor. Shimizu, M., Potts, J.T., Gardella, T.J. J. Biol. Chem. (2000) [Pubmed]
  25. Selective and nonselective inverse agonists for constitutively active type-1 parathyroid hormone receptors: evidence for altered receptor conformations. Carter, P.H., Petroni, B.D., Gensure, R.C., Schipani, E., Potts , J.T., Gardella, T.J. Endocrinology (2001) [Pubmed]
  26. Short-term effects of synthetic human parathyroid hormone-(1--34) administration on bone mineral metabolism in osteoporotic patients. Slovik, D.M., Neer, R.M., Potts, J.T. J. Clin. Invest. (1981) [Pubmed]
  27. Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial. Lane, N.E., Sanchez, S., Modin, G.W., Genant, H.K., Pierini, E., Arnaud, C.D. J. Clin. Invest. (1998) [Pubmed]
  28. Teriparatide [PTH(1-34)] strengthens the proximal femur of ovariectomized nonhuman primates despite increasing porosity. Sato, M., Westmore, M., Ma, Y.L., Schmidt, A., Zeng, Q.Q., Glass, E.V., Vahle, J., Brommage, R., Jerome, C.P., Turner, C.H. J. Bone Miner. Res. (2004) [Pubmed]
  29. Circulating intact parathyroid hormone measured by a two-site immunochemiluminometric assay. Brown, R.C., Aston, J.P., Weeks, I., Woodhead, J.S. J. Clin. Endocrinol. Metab. (1987) [Pubmed]
WikiGenes - Universities