The Parathyroid Hormone Molecule: Biological Implications of Structure

  • Michael Rosenblatt
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 151)


Analysis of the relation of structure to hormonal function for parathyroid hormone (PTH) has provided important insights into the physiological roles served by certain regions of the hormone molecule and the initial events and mechanisms by which hormonal messages are translated into physiological actions. Chemical synthesis of multiple segments of the hormone has now been achieved. Thus far approximately 80 analogues or fragments of PTH have been synthesized. Taken together, these synthetic fragments comprise (with considerable overlap) the entire structure of pre-proparathyroid hormone (Pre-ProPTH) and multiple analogues of the active core.


Parathyroid Hormone Rough Endoplasmic Reticulum Leader Sequence Agonist Property Human Parathyroid Hormone 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    G. Blobel and D.D. Sabatini, Ribosorne-membrane interaction in eukaryotic cells, Biomembranes. 2:193 (1971).CrossRefGoogle Scholar
  2. 2.
    C. Milstein, G.G. Brownlee, T.M. Harrison and M.B. Mathews, A possible precursor of immunoglobulin light chains, Nature New Biol. 239:117 (1972).PubMedCrossRefGoogle Scholar
  3. 3.
    M. Rosenblatt, J.F. Habener, G.A. Tyler, G.L. Shepard, and J.T. Potts Jr., Chemical synthesis of the precursor-specific region of pre-proparathyroid hormone, J. Biol. Chem. 254:1414 (1979).PubMedGoogle Scholar
  4. 4.
    J.A. Majzoub, M. Rosenblatt, B. Fennick, R. Maunus, H.M. Kronenberg, J.T. Potts Jr. and J.F. Habener, Synthetic preproparathyroid hormone leader sequence inhibits cell-free processing of placental, parathyroid, and pituitary prehormones, J. Biol. Chem. 255:11478 (1980).PubMedGoogle Scholar
  5. 5.
    G.W. Tregear, J. van Rietschoten, E. Greene, H.T. Keutmann, H.D. Niall, B. Reit, J.A. Parsons and J.T. Potts Jr., Bovine parathyroid hormone: minimum chain length of synthetic peptide required for biological activity, Endocrinology 93:1349 (1973).PubMedCrossRefGoogle Scholar
  6. 6.
    M. Rosenblatt, Parathyroid hormone: chemistry and structure—activity relations, Pathobiol. Annu. (in press).Google Scholar
  7. 7.
    R.A. Nissenson and CD. Arnaud, Properties of the parathyroid hormone receptor-adenylate cyclase system in chicken renal plasma membranes, J. Biol. Chem. 254:1469 (1979).PubMedGoogle Scholar
  8. 8.
    G.W. Segre, M. Rosenblatt, B.L. Reiner, J.E. Mahaffey and J.T. Potts Jr., Characterization of parathyroid hormone receptors in canine renal cortical plasma membranes using a radioiodinated sulfur-free hormone analogue: correlation of binding with adenylate cyclase activity, J. Biol. Chem. 254:6980 (1979).PubMedGoogle Scholar
  9. 9.
    M. Rosenblatt, G.V. Segre and J.T. Potts Jr., Synthesis of a fragment of parathyroid hormone, bPTH-(28–48): an inhibitor of hormone cleavage in vivo, Biochemistry 16:2811 (1977).PubMedCrossRefGoogle Scholar
  10. 10.
    M. Rosenblatt, H.T. Keutmann, G.W. Tregear and J.T. Potts Jr., Synthesis of a fragment of human parathyroid hormone, bPTH-(44–68), J. Med. Chem. 20:1452 (1977).PubMedCrossRefGoogle Scholar
  11. 11.
    M. Rosenblatt, G.V. Segre, G.W. Tregear, G.L. Shepard, G.A. Tyler and J.T. Potts Jr., Human parathyroid hormone: synthesis, chemical, biological, and immunological evaluation of the carboxyl-terminal region, Endocrinology 103:978 (1978).PubMedCrossRefGoogle Scholar
  12. 12.
    M.P.M. Herrmann-Erlee, J.N.M. Heersche, J.W. Hekkelman, P.J. Gaillard, G.W. Tregear, J.A. Parsons and J.T. Potts, Jr., Effects on bone in vitro of bovine parathyroid hormone and synthetic fragments representing residues 1–34, 2–34, and 3–34, Endocrine Res. Commun. 3:21 (1976).CrossRefGoogle Scholar
  13. 13.
    J.A. Parsons, B. Rafferty, D. Gray, B. Reit, J.M. Zanelli, H.T. Keutmann, G.W. Tregear, E.N. Callahan and J.T. Potts Jr., Pharmacology of parathyroid hormone and some of its fragments and analogues, in: “Calcium-Regulating Hormones: Proceedings of the Fifth Parathyroid Conference”, R.V. Talmage, M. Owen and J.A. Parsons, eds., Excerpta Medica, Amsterdam (1975).Google Scholar
  14. 14.
    G.W. Tregear and J.T. Potts Jr., Synthetic analogues of residues 1–34 of human parathyroid hormone: influence of residue number 1 on biological potency in vitro, Endocrine Res. Commun. 2:561 (1975).CrossRefGoogle Scholar
  15. 15.
    M. Rosenblatt, D. Goltzman, H.T. Keutmann, G.W. Tregear and J.T. Potts Jr., Chemical and biological properties of synthetic sulfur-free analogues of parathyroid hormone, J. Biol. Chem. 251:159 (1976).PubMedGoogle Scholar
  16. 16.
    M. Rosenblatt and J.T. Potts Jr., Design and synthesis of parathyroid hormone analogues of enhanced biological activity, Endocrine Res. Commun. 4:115 (1977).CrossRefGoogle Scholar
  17. 17.
    M. Rosenblatt, M.D. Coltrera, G.L. Shepard, D.A. Gray, J.A. Parsons and J.T. Potts Jr., Sulfur-free parathyroid hormone analogues containing D-amino acids: biological properties in vitro and in vivo, Biochemistry (in press).Google Scholar
  18. 18.
    M.D. Coltrera, J.T. Potts, Jr. and M. Rosenblatt, Identification of a renal receptor for parathyroid hormone by photoaffinity radiolabeling using a synthetic analogue, J. Biol. Chem. (in press).Google Scholar
  19. 19.
    M. Rosenblatt, E.N. Callahan, J.E. Mahaffey, A. Pont and J.T. Potts Jr, Parathyroid hormone inhibitors: design, synthesis, and biologic evaluation of hormone analogues, J. Biol. Chem. 252:5847 (1977).PubMedGoogle Scholar
  20. 20.
    S.R. Goldring, J.E. Mahaffey, M. Rosenblatt, J.-M. Dayer, J.T. Potts Jr. and S.M Krane, Parathyroid hormone inhibitors: comparison of biological activity in bone- and skin-derived tissue, J. Clin. Endocrinol. Metab. 48:655 (1979).PubMedCrossRefGoogle Scholar
  21. 21.
    D.A. Gray, J.A. Parsons, J.T. Potts Jr., M. Rosenblatt and R.W. Stevenson, In vivo testing of a parathyroid hormone antagonist, [N1e-8, N1e-18, Tyr-34]bPTH-(3–34)amide, Br. J. Pharmacol, (submitted).Google Scholar
  22. 22.
    G.V. Segre, G. Tully, M. Rosenblatt, J. Laugharn, B. Reit and J.T. Potts Jr., Evaluation of an in vitro parathyroid hormone (bPTH) antagonist in intact dogs, Calcif. Tissue Int. 28:171 (1979) (Abstr).Google Scholar
  23. 23.
    M. Rosenblatt, G.V. Segre, G.A. Tyler, G.L. Shepard, S.R. Nussbaum and J.T. Potts Jr., Identification of a receptor-binding region in parathyroid hormone, Endocrinology, 106:545 (1980).CrossRefGoogle Scholar
  24. 24.
    S.R. Nussbaum, M. Rosenblatt and J.T. Potts Jr., Parathyroid hormone-renal receptor interactions: demonstration of two receptor-binding domains, J. Biol. Chem. 255:10183 (1980).PubMedGoogle Scholar
  25. 25.
    K.J. Martin, J.J. Freitag, M.B. Conrades, K.A Hruska, S. Klahr and E. Slatopolsky, Selective uptake of the synthetic amino terminal fragment of bovine parathyroid hormone by isolated perfused bone, J. Clin. Invest. 62:256 (1978).PubMedCrossRefGoogle Scholar
  26. 26.
    D. Goltzman, Examination of the requirement for metabolism of parathyroid hormone in skeletal tissue before biological action, Endocrinology 102:1555 (1978).PubMedCrossRefGoogle Scholar
  27. 27.
    G.V. Segre, H.D. Niall, J.F. Habener and J.T. Potts Jr., Metabolism of parathyroid hormone: physiologic and clinical significance, Am. J. Med. 56:774 (1974).PubMedCrossRefGoogle Scholar
  28. 28.
    P. D’Amour, P.M. Huet, G.V. Segre, and M. Rosenblatt, Charactersitics of bovine parathyroid hormone extraction by the dog liver in vivo, Am.J. Physiol, (in press).Google Scholar
  29. 29.
    S.G. Massry, E. Bogin, D. Meytes, G. Bristol, J. Smith and P.P. Dukes, Effect of parathyroid hormone (PTH) on red blood cells (RBC) and on erythropoiesis, Clin. Res. 28:535A (1980).Google Scholar
  30. 30.
    D. Meytes, E. Bogin, A. Ma, P.P. Dukes and S.G. Massry, Effect of parathyroid hormone on erythropoiesis, J. Clin. Invest. 67:1263 (1981).PubMedCrossRefGoogle Scholar
  31. 31.
    A.J. Erslev, T. Connelly and J. Caro, The role of parathyroid hormones in erythropoiesis, in: “Proceedings of The Conference on Aplastic Anemia: A Stem Cell Disease,” A.S. Levine, ed., U.S. Dept. of Health and Human Services, National Institutes of Health, N.I.H. Publication No. 81–1008 (1981).Google Scholar
  32. 32.
    J. Misiti and J.L. Spivak, Erythropoiesis in vitro, J. Clin. Invest. 64:1573 (1979).PubMedCrossRefGoogle Scholar
  33. 33.
    E. Bogin, S.G. Massry and I. Harary, Effect of parathyroid hormone on rat heart cells, J. Clin. Invest. 67:1215 (1981).PubMedCrossRefGoogle Scholar
  34. 34.
    K.A. Hruska, J. Blondin, R. Bass, J. Santiago, L. Thomas, P. Altsheler, K. Martin and S. Klahr, Effect of intact parathyroid hormone on hepatic glucose release in the dog. J. Clin. Invest. 64:1016 (1979).PubMedCrossRefGoogle Scholar
  35. 35.
    J.M. Canterbury, G. Levy, E. Ruiz and E. Reiss, Parathyroid hormone activation of adenylate cyclase in liver, Proc. Soc. Exp. Biol. Med. 147:366 (1974).PubMedGoogle Scholar
  36. 36.
    M.A. Moxley, N.H. Bell, S.R. Wagle, D.O. Allen and J. Ashmore, Parathyroid hormone stimulation of glucose and urea production in isolated liver cells, Am. J. Physiol. 227:1058 (1974).PubMedGoogle Scholar
  37. 37.
    C.E. Arber, J.M. Zanelli, J.A. Parsons, L. Bitensky and J. Chayen, Comparison of the bioactivity of highly purified human parathyroid hormone and of synthetic amino- and carboxyl-region fragments, J. Endocrinol. 85:55P (1980).Google Scholar

Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • Michael Rosenblatt
    • 1
  1. 1.Endocrine UnitMassachusetts General HospitalBostonUSA

Personalised recommendations