Skip to main content

Toward an Understanding of Human Parathyroid Hormone Structure and Function

  • Chapter
Molecular Biology of the Parathyroid

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Potts JT Jr, Bringhurst FR, Gardella TJ et al. Endocrinology; Parathyroid Hormone: Physiology, Chemistry, Biosynthesis, Secretion, Metabolism and Mode of Action. Philadelphia: W.B. Saunders Company, 1995:920–966.

    Google Scholar 

  2. Gardella TJ JŸppner H. Interaction of PTH and PTHrP with their receptors. Rev Endocine & Metab Disorders 2000; 1:317–329.

    Article  CAS  Google Scholar 

  3. Canalis E, Hock JM Raisz LG. The Parathyriods. New York: Raven Press, 1994:65–82.

    Google Scholar 

  4. Neer RM, Arnaud CD, Zanchetta JR et al. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001; 344:1434–1441.

    Article  PubMed  CAS  Google Scholar 

  5. Chase LR, Aurbach GD. The effect of parathyroid hormone on the concentration of adenosine 3′,5′-monophosphate in skeletal tissue in vitro. J Biol Chem 1970; 245:1520–1526.

    PubMed  CAS  Google Scholar 

  6. Civitelli R, Reid IR, Westbrook S et al. Parathyroid hormone depresses cytosolic pH and DNA synthesis in osteoblast-like cells. Am J Physiol 1988; 255:E660–667.

    PubMed  CAS  Google Scholar 

  7. Mosekilde L, Sogaard CH, Danielsen CC et al. The anabolic effects of human parathyroid hormone (hPTH) on rat vertebral body mass are also reflected in the quality of bone, assessed by biomechanical testing: A comparison study between hPTH-(1–34) and hPTH-(1–84). Endocrinology 1991; 129:421–428.

    PubMed  CAS  Google Scholar 

  8. Brommage R, Hotchkiss CE, Lees CJ et al. Daily treatment with human recombinant parathyroid hormone-(1-34), LY333334, for 1 year increases bone mass in ovariectomized monkeys. J Clin Endocrinol Metab 1999; 84:3757–3763.

    Article  PubMed  CAS  Google Scholar 

  9. Lindsay R, Nieves J, Formica C et al. Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet 1997; 350:550–555.

    Article  PubMed  CAS  Google Scholar 

  10. Mitlak BH. Parathyroid hormone as a therapeutic agent. Curr Opin Pharmacol 2002; 2:694–699.

    Article  PubMed  CAS  Google Scholar 

  11. Rubin MR, Bilezikian JP. The potential of parathyroid hormone as a therapy for osteoporosis. Int J Fertil Womens Med 2002; 47:103–115.

    PubMed  CAS  Google Scholar 

  12. Tregear GW, Van Rietschoten J, Greene E et al. Bovine parathyroid hormone: minimum chain length of synthetic peptide required for biological activity. Endocrinology 1973; 93:1349–1353.

    Article  PubMed  CAS  Google Scholar 

  13. Gardella TJ, Axelrod D, Rubin D et al. Mutational analysis of the receptor-activating region of human parathyroid hormone. J Biol Chem 1999; 266:13141–13146.

    Google Scholar 

  14. Jüppner H, Schipani E, Bringhurst FR et al. The extracellular amino-terminal region of the parathyroid hormone (PTH)/PTH-related peptide receptor determines the binding affinity for carboxyl-terminal fragments of PTH-(1-34). Endocrinology 1 1994; 134:879–884.

    Article  Google Scholar 

  15. Moseley JM, Gillespie MT. Parathyroid hormone-related protein. Crit Rev Clin Lab Sci 1995; 32:299–343.

    PubMed  CAS  Google Scholar 

  16. Blind E, Raue F, Knappe V et al. Cyclic AMP formation in rat bone and kidney cells is stimulated equally by parathyroid hormone-related protein (PTHrP) 1-34 and PTH 1-34. Exp Clin Endocrinol 1993; 101:150–155.

    Article  PubMed  CAS  Google Scholar 

  17. Gronwald W, Schomburg D, Tegge W et al. Assessment by 1H NMR spectroscopy of the structural behaviour of human parathyroid-hormone-related protein (1–34) and its close relationship with the N-terminal fragments of human parathyroid hormone in solution. Biol Chem 1997;378:1501–1508.

    Article  PubMed  CAS  Google Scholar 

  18. Weidler M, Marx UC, Seidel G et al. The structure of human parathyroid hormone-related protein(1–34) in near-physiological solution. FEBS Lett 1999; 444:239–244.

    Article  PubMed  CAS  Google Scholar 

  19. Piserchio A., Usdin T, Mierke DF. Structure of tuberoinfundibular peptide of 39 residues. J Biol Chem 2000; 275:27284–27290.

    PubMed  CAS  Google Scholar 

  20. Usdin TB, Bonner TI, Hoare SR. The parathyroid hormone 2 (PTH2) receptor. Receptors Channels 2002; 8:211–218.

    Article  PubMed  CAS  Google Scholar 

  21. Jonsson KB, John MR, Gensure RC et al. Tuberoinfundibular peptide 39 binds to the parathyroid hormone (PTH)/PTH-related peptide receptor, but functions as an antagonist. Endocrinology 2001; 142:704–709.

    Article  PubMed  CAS  Google Scholar 

  22. Fiskin AM, Cohn DV, Peterson GS. A model for the structure of bovine parathormone derived by dark field electron microsocpy. J Biol Chem 1997; 252:8261–8268.

    Google Scholar 

  23. Marx UC, Austermann S, Bayer P et al. Structure of human parathyroid hormone 1–37 in solution. J Biol Chem 1995; 270:15194–15202.

    Article  PubMed  CAS  Google Scholar 

  24. Barden JA, Kemp BE. NMR solution structure of human parathyroid hormone(1–34). Biochemistry 1993; 32:7126–7132.

    Article  PubMed  CAS  Google Scholar 

  25. Klaus W, Dieckmann T, Wray V et al. Investigation of the solution structure of the human parathyroid hormone fragment (1–34) by 1H NMR spectroscopy, distance geometry, and molecular dynamics calculations. Biochemistry 1991; 30:6936–6942.

    Article  PubMed  CAS  Google Scholar 

  26. Strickland LA, Bozzato RP, Kronis KA. Structure of human parathyroid hormone(1–34) in the presence of solvents and micelles. Biochemistry 1993; 32:6050–6057.

    Article  PubMed  CAS  Google Scholar 

  27. Chorev M, Behar V, Yang Q et al. Conformation of parathyroid hormone antagonists by CD, NMR, and molecular dynamics simulations. Biopolymers 1995; 36:485–495.

    Article  PubMed  CAS  Google Scholar 

  28. Pellegrini M, Royo M, Rosenblatt M et al. Addressing the tertiary structure of human parathyroid hormone-(1–34). J Biol Chem 1998; 273:10420–10427.

    Article  PubMed  CAS  Google Scholar 

  29. Neugebauer W, Surewicz WK, Gordon HL et al. Structural elements of human parathyroid hormone and their possible relation to biological activities. Biochemistry 1992; 31:2056–2063.

    Article  PubMed  CAS  Google Scholar 

  30. Jin L, Briggs SL, Chandrasekhar S et al. Crystal structure of human parathyroid hormone 1–34 at 0.9-A resolution. J Biol Chem 2001; 275:27238–27244.

    Google Scholar 

  31. Jones TA, Kjeldgaard M. Electron-density map interpretation. Methods Enzymol 1997; 277:173–208.

    Article  CAS  PubMed  Google Scholar 

  32. Brunger AT. X-PLOR version 3.1: A system for crystallography and N MR. New Haven: Yale University Press, 1993.

    Google Scholar 

  33. Sheldrick GM, Schneider TR. SHELXL: High-resolution refinement. Methods Enzymol 1997; 277:319–343.

    CAS  PubMed  Google Scholar 

  34. Chorev M, Goldman ME, McKee RL et al. Modifications of position 12 in parathyroid hormone and parathyroid hormone related protein: Toward the design of highly potent antagonists. Biochemistry 1993; 29:1580–1586.

    Article  Google Scholar 

  35. Gronwald W, Schomburg D, Harder MPF et al. Structure of recombinant human parathyroid hormone in solution using multidimensional NMR spectroscopy. Biol Chem Hoppe-Seyler 1996; 377:175–186.

    PubMed  CAS  Google Scholar 

  36. Chen Z, Xu P, Barbier J-R et al. Solution structure of the osteogenic 1–31 fragment of the human parathyroid hormone. Biochemistry 2000; 39:12766–12777.

    Article  PubMed  CAS  Google Scholar 

  37. Marx UC, Adermann K, Bayer P et al. Solution structures of human parathyroid hormone fragments hPTH(1–34) and hPTH(1–39) and bovine parathyroid hormone fragment bPTH(1–37). Biochem Biophys Res Comm 2000; 267:213–220.

    Article  PubMed  CAS  Google Scholar 

  38. Wray V, Federau T, Gronwald W et al. The structure of human parathyroid hormone from a study of fragments in solution using 1H NMR spectroscopy and its biological implications. Biochemistry 1994; 33:1684–1693.

    Article  PubMed  CAS  Google Scholar 

  39. Luecke H, Schobert B, Lanyi JK et al. Crystal structure of sensory rhodopsin II at 2.4 angstroms: Insights into color tuning and transducer interaction. Science; 293:1499–1503.

    Google Scholar 

  40. Archer E, Maigret B, Esrieut C et al. Rhodopsin crystal: New template yielding realistic models of G-protein-coupled receptors? Trends Pharmacol Sci 2003; 24:36–40.

    Article  PubMed  CAS  Google Scholar 

  41. Belrhali H, Nollert P, Royant A et al. Protein, lipid and water organization in bacteriorhodopsin crystals: A molecular view of the purple membrane at 1.9 A resolution. Structure Fold Des 1999; 7:909–917.

    Article  PubMed  CAS  Google Scholar 

  42. Pellegrini M, Bisello A, Rosenblatt M et al. Binding domain of human parathyroid hormone receptor: From conformation to function. Biochemistry 1998; 37:12737–12743.

    Article  PubMed  CAS  Google Scholar 

  43. Bisello A, Adams AE, Mierke DF et al. Parathyroid hormone-receptor interactions identified directly by photocross-linking and molecular modeling studies. J Biol Chem 1998; 273:22498–22505.

    Article  PubMed  CAS  Google Scholar 

  44. Adams AE, Bisello A, Chorev M et al. 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. Mol Endocrinol 1998; 12:1673–1683.

    Article  PubMed  CAS  Google Scholar 

  45. Chorev M, Rosenblatt M. Principle of Bone Biology. San Diego: Academic Press, 1996.

    Google Scholar 

  46. Gensure RC, Gardella TJ, Juppner H. Multiple sites of contact between the carboxyl-terminal binding domain of PTHrP-(1–36) analogs and the amino-terminal extracellular domain of the PTH/PTHrP receptor identified by photoaffinity cross-linking. J Biol Chem 2001; 276:28650–28658.

    Article  PubMed  CAS  Google Scholar 

  47. Gardella TJ, Wilson AK, Keutmann HT et al. Analysis of parathyroid hormone’s principal receptor-binding region by site-directed mutagenesis and analog design. Endocrinology 1993; 132:2024–2030.

    Article  PubMed  CAS  Google Scholar 

  48. Rolz C, Pellegrini M, Mierke DF. Molecular characterization of the receptor-ligand complex for parathyroid hormone. Biochemistry 1999; 38:6397–6405.

    Article  PubMed  CAS  Google Scholar 

  49. Vickery BH, Avnur Z, Cheng Y et al. RS-66271, a C-tcrminally substituted analog of human parathyroid hormone-related protein (1–34), increases trabecular and cortical bone in ovariectomized, osteopenic rats. J Bone Miner Res 1996; 11:1943–1951.

    Article  PubMed  CAS  Google Scholar 

  50. Pellegrini M, Bisello A, Rosenblatt M et al. Conformational studies of RS-66271, an analog of parathyroid hormone-related protein with pronounced bone anabolic activity. J Med Chem 1997; 40:3025–3031.

    Article  PubMed  CAS  Google Scholar 

  51. Condon SM, Morize I, Darnbrough S et al. The bioactive conformation of human parathyroid hormone. Structural evidence for the extended helix postulate. J Am Chem Soc 2001; 122:3007–3014.

    Article  CAS  Google Scholar 

  52. Mierke DF, Maretto S, Schievano E et al. Conformational studies of mono-and bicyclic parathyroid hormone-related protein-derived agonists. Biochemistry 1997; 36:10372–10383.

    Article  PubMed  CAS  Google Scholar 

  53. Takasu H, Gardella TJ, Luck MD et al. Amino-terminal modifications of human parathyroid hormone (PTH) selectively alter phospholipase C signaling via the type 1 PTH receptor: Implications for design of signal-specific PTH ligands. Biochemistry 1999; 38:13453–13460.

    Article  PubMed  CAS  Google Scholar 

  54. Behar V, Nakamoto C, Greenberg Z et al. Histidine at position 5 is the specificity “switch” between two parathyroid hormone receptor subtypes. Endocrinology 1996; 137:4217–4224.

    Article  PubMed  CAS  Google Scholar 

  55. Gardella TJ, Luck MD, Jensen GS et al. Converting parathyroid hormone-related peptide (PTHrP) into a potent PTH-2 receptor agonist. J Biol Chem 1996; 271:19888–19893.

    Article  PubMed  CAS  Google Scholar 

  56. Tashjian AH, Jr., Ontjes DA, Munson PL. Alkylation and oxidation of methionine in bovine parathyroid hormone: Effects on hormonal activity and antigenicity. Biochemistry 1964; 3:1175–1182.

    Article  PubMed  Google Scholar 

  57. Frelinger A.L, III, Zull JE. The role of the methionine residues in the structure and function of parathyroid hormone. Arch Biochem Biophys 1986; 244:641–649.

    Article  PubMed  CAS  Google Scholar 

  58. Reidhaar-Olson JF, Davis RM, De Souza-Hart JA et al. Active variants of human parathyroid hormone (1–34) with multiple amino acid substitutions. Mol Cell Endocrinol 2000; 160:135–147.

    Article  PubMed  CAS  Google Scholar 

  59. Fraher LJ, Avram R, Watson PH et al. Comparison of the biochemical responses to human parathyroid hormone-(1–31)NH2 and hPTH-(1–34) in healthy humans. J Clin Endocrinol Metab 1999; 84:2739–2743.

    Article  PubMed  CAS  Google Scholar 

  60. Whitfield JF, Morley P, Willick G et al. Cyclization by a specific lactam increases the ability of human parathyroid hormone (hPTH)-(1–31)NH2 to stimulate bone growth in ovariectomized rats. J Bone Mineral Res 1997; 12:1246–1252.

    Article  CAS  Google Scholar 

  61. Barbier J-R, Maclean S, Morley P et al. Structure and activities of constrained analogues of human parathyroid hormone and parathyroid hormone-related peptide: implications for receptor-activating conformations of the hormones. Biochemistry 2000; 39:14522–14530.

    Article  PubMed  CAS  Google Scholar 

  62. Shimizu M, Shimizu N, Tsang JC et al. Residue 19 of the parathyroid hormone (PTH) modulates ligand interaction with the juxtamembrane region of the PTH-1 receptor. Biochemistry 2002; 41:13224–13233.

    Article  PubMed  CAS  Google Scholar 

  63. Piserchio A, Shimizu N, Gardella TJ et al. Residue 19 of the parathyroid hormone: Structural consequences. Biochemistry 2002; 41:13217–13223.

    Article  PubMed  CAS  Google Scholar 

  64. Barbier J-R, MacLean S, Whitfield JF et al. Structural requirements for conserved arginine of parathyroid hormone. Biochemistry 2001; 40:8955–8961.

    Article  PubMed  CAS  Google Scholar 

  65. Shimizu M, Potts JT, Jr., Gardella T. Minimization of parathyroid hormone. Novel amino-terminal parathyroid hormone fragments with enhanced potency in activating the type-1 parathyroid hormone receptor. J Biol Chem 2000; 275:21836–21843.

    Article  PubMed  CAS  Google Scholar 

  66. Shimizu M, Carter PH, Khatri A et al. Enhanced activity in parathyroid hormone-(1–l4) and-(1–11): Novel peptides for probing ligand-receptor interactions. Endocrinology 2001; 142:3068–3074.

    Article  PubMed  CAS  Google Scholar 

  67. Shimizu N, Guo J, Gardella TJ. Parathyroid hormone (PTH)-(1–14) and-(1–11) analogs conformationally constrained by alpha-aminoisobutyric acid mediate full agonist responses via the juxtamembrane region of the PTH-1 receptor. J Biol Chem 2001; 276:49003–49012.

    Article  PubMed  CAS  Google Scholar 

  68. Jung J, Lim S-K, Kim Y et al. NMR structure of a minimum activity domain of human parathyroid peptide hormone: Structural origin of receptor activation. J Peptide Res 2002; 60:239–246.

    Article  CAS  Google Scholar 

  69. Shimizu N, Petroni BD, Khatri A et al. Functional evidence for an intramolecular side chain interaction between residues 6 and 10 of receptor-bound parathyroid hormone analogues. Biochemistry 2003; 42:2282–2290.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Eurekah.com and Kluwer Academic / Plenum Publishers

About this chapter

Cite this chapter

Jin, L., Tashjian, A.H., Zhang, F. (2005). Toward an Understanding of Human Parathyroid Hormone Structure and Function. In: Molecular Biology of the Parathyroid. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27530-4_3

Download citation

Publish with us

Policies and ethics