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. 1998 Jan;152(1):17–21.

Parathyroid-hormone-related protein in sarcoidosis.

H J Zeimer 1, T M Greenaway 1, J Slavin 1, D K Hards 1, H Zhou 1, J C Doery 1, A N Hunter 1, A Duffield 1, T J Martin 1, V Grill 1
PMCID: PMC1858120  PMID: 9422518

Abstract

Parathyroid-hormone-related protein (PTHrP) is the main mediator of the humoral hypercalcemia of malignancy. It is also detected in many normal adult and fetal tissues. Altered calcium metabolism occurs in sarcoidosis, and two cases of sarcoidosis with hypercalcemia and elevated plasma PTHrP are described. An archival study of 20 lymph node biopsies with the pathological diagnosis of sarcoidosis was performed. Immunohistochemistry using a polyclonal antiserum to human PTHrP and in situ hybridization using a riboprobe to human PTHrP were performed on the lymph node biopsies. Immunohistochemistry for PTHrP was also performed on the biopsies from the two cases with elevated plasma levels. Immunohistochemical analysis detected PTHrP in macrophages within granulomata in 17 of the 20 (85%) biopsies. In situ hybridization detected a positive signal for messenger RNA in the granulomata of 11 of 19 (58%) biopsies. PTHrP immunoreactivity and PTHrP gene expression are present in sarcoid granulomata. PTHrP may contribute to the hypercalcemia of sarcoidosis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams J. S., Gacad M. A., Diz M. M., Nadler J. L. A role for endogenous arachidonate metabolites in the regulated expression of the 25-hydroxyvitamin D-1-hydroxylation reaction in cultured alveolar macrophages from patients with sarcoidosis. J Clin Endocrinol Metab. 1990 Mar;70(3):595–600. doi: 10.1210/jcem-70-3-595. [DOI] [PubMed] [Google Scholar]
  2. Adams J. S., Sharma O. P., Gacad M. A., Singer F. R. Metabolism of 25-hydroxyvitamin D3 by cultured pulmonary alveolar macrophages in sarcoidosis. J Clin Invest. 1983 Nov;72(5):1856–1860. doi: 10.1172/JCI111147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barbour G. L., Coburn J. W., Slatopolsky E., Norman A. W., Horst R. L. Hypercalcemia in an anephric patient with sarcoidosis: evidence for extrarenal generation of 1,25-dihydroxyvitamin D. N Engl J Med. 1981 Aug 20;305(8):440–443. doi: 10.1056/NEJM198108203050807. [DOI] [PubMed] [Google Scholar]
  4. Bost T. W., Riches D. W., Schumacher B., Carré P. C., Khan T. Z., Martinez J. A., Newman L. S. Alveolar macrophages from patients with beryllium disease and sarcoidosis express increased levels of mRNA for tumor necrosis factor-alpha and interleukin-6 but not interleukin-1 beta. Am J Respir Cell Mol Biol. 1994 May;10(5):506–513. doi: 10.1165/ajrcmb.10.5.8179912. [DOI] [PubMed] [Google Scholar]
  5. Bucht E., Eklund A., Toss G., Lewensohn R., Granberg B., Sjöstedt U., Eddeland R., Tørring O. Parathyroid hormone-related peptide, measured by a midmolecule radioimmunoassay, in various hypercalcaemic and normocalcaemic conditions. Acta Endocrinol (Copenh) 1992 Oct;127(4):294–300. doi: 10.1530/acta.0.1270294. [DOI] [PubMed] [Google Scholar]
  6. Danks J. A., Ebeling P. R., Hayman J., Chou S. T., Moseley J. M., Dunlop J., Kemp B. E., Martin T. J. Parathyroid hormone-related protein: immunohistochemical localization in cancers and in normal skin. J Bone Miner Res. 1989 Apr;4(2):273–278. doi: 10.1002/jbmr.5650040221. [DOI] [PubMed] [Google Scholar]
  7. Firkin F., Seymour J. F., Watson A. M., Grill V., Martin T. J. Parathyroid hormone-related protein in hypercalcaemia associated with haematological malignancy. Br J Haematol. 1996 Sep;94(3):486–492. doi: 10.1046/j.1365-2141.1996.d01-1819.x. [DOI] [PubMed] [Google Scholar]
  8. Grill V., Ho P., Body J. J., Johanson N., Lee S. C., Kukreja S. C., Moseley J. M., Martin T. J. Parathyroid hormone-related protein: elevated levels in both humoral hypercalcemia of malignancy and hypercalcemia complicating metastatic breast cancer. J Clin Endocrinol Metab. 1991 Dec;73(6):1309–1315. doi: 10.1210/jcem-73-6-1309. [DOI] [PubMed] [Google Scholar]
  9. Heath J. K., Southby J., Fukumoto S., O'Keeffe L. M., Martin T. J., Gillespie M. T. Epidermal growth factor-stimulated parathyroid hormone-related protein expression involves increased gene transcription and mRNA stability. Biochem J. 1995 Apr 1;307(Pt 1):159–167. doi: 10.1042/bj3070159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Henson D. E. Loss of p53-immunostaining intensity in breast cancer. J Natl Cancer Inst. 1996 Aug 7;88(15):1015–1016. doi: 10.1093/jnci/88.15.1015. [DOI] [PubMed] [Google Scholar]
  11. Horiuchi N., Caulfield M. P., Fisher J. E., Goldman M. E., McKee R. L., Reagan J. E., Levy J. J., Nutt R. F., Rodan S. B., Schofield T. L. Similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro. Science. 1987 Dec 11;238(4833):1566–1568. doi: 10.1126/science.3685994. [DOI] [PubMed] [Google Scholar]
  12. Mason R. S., Frankel T., Chan Y. L., Lissner D., Posen S. Vitamin D conversion by sarcoid lymph node homogenate. Ann Intern Med. 1984 Jan;100(1):59–61. doi: 10.7326/0003-4819-100-1-59. [DOI] [PubMed] [Google Scholar]
  13. Pandian M. R., Morgan C. H., Carlton E., Segre G. V. Modified immunoradiometric assay of parathyroid hormone-related protein: clinical application in the differential diagnosis of hypercalcemia. Clin Chem. 1992 Feb;38(2):282–288. [PubMed] [Google Scholar]
  14. Papapoulos S. E., Clemens T. L., Fraher L. J., Lewin I. G., Sandler L. M., O'Riordan J. L. 1, 25-dihydroxycholecalciferol in the pathogenesis of the hypercalcaemia of sarcoidosis. Lancet. 1979 Mar 24;1(8117):627–630. doi: 10.1016/s0140-6736(79)91076-6. [DOI] [PubMed] [Google Scholar]
  15. Reichel H., Koeffler H. P., Barbers R., Norman A. W. Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis. J Clin Endocrinol Metab. 1987 Dec;65(6):1201–1209. doi: 10.1210/jcem-65-6-1201. [DOI] [PubMed] [Google Scholar]
  16. Reiner M., Sigurdsson G., Nunziata V., Malik M. A., Poole G. W., Joplin G. F. Abnormal calcium metabolism in normocalcaemic sarcoidosis. Br Med J. 1976 Dec 18;2(6050):1473–1476. doi: 10.1136/bmj.2.6050.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rizzoli R., Feyen J. H., Grau G., Wohlwend A., Sappino A. P., Bonjour J. P. Regulation of parathyroid hormone-related protein production in a human lung squamous cell carcinoma line. J Endocrinol. 1994 Nov;143(2):333–341. doi: 10.1677/joe.0.1430333. [DOI] [PubMed] [Google Scholar]
  18. Roskams T., Desmet V. Parathyroid-hormone-related peptides. A new class of multifunctional proteins. Am J Pathol. 1997 Mar;150(3):779–785. [PMC free article] [PubMed] [Google Scholar]
  19. Schweitzer D. H., Hamdy N. A., Frölich M., Zwinderman A. H., Papapoulos S. E. Malignancy-associated hypercalcaemia: resolution of controversies over vitamin D metabolism by a pathophysiological approach to the syndrome. Clin Endocrinol (Oxf) 1994 Aug;41(2):251–256. doi: 10.1111/j.1365-2265.1994.tb02538.x. [DOI] [PubMed] [Google Scholar]
  20. Sharma O. P. Vitamin D, calcium, and sarcoidosis. Chest. 1996 Feb;109(2):535–539. doi: 10.1378/chest.109.2.535. [DOI] [PubMed] [Google Scholar]
  21. Sternberger L. A., Hardy P. H., Jr, Cuculis J. J., Meyer H. G. The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem. 1970 May;18(5):315–333. doi: 10.1177/18.5.315. [DOI] [PubMed] [Google Scholar]
  22. Walker A. T., Stewart A. F., Korn E. A., Shiratori T., Mitnick M. A., Carpenter T. O. Effect of parathyroid hormone-like peptides on 25-hydroxyvitamin D-1 alpha-hydroxylase activity in rodents. Am J Physiol. 1990 Feb;258(2 Pt 1):E297–E303. doi: 10.1152/ajpendo.1990.258.2.E297. [DOI] [PubMed] [Google Scholar]
  23. Walker C., Bauer W., Braun R. K., Menz G., Braun P., Schwarz F., Hansel T. T., Villiger B. Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. Am J Respir Crit Care Med. 1994 Oct;150(4):1038–1048. doi: 10.1164/ajrccm.150.4.7921434. [DOI] [PubMed] [Google Scholar]
  24. Zhou H., Choong P., McCarthy R., Chou S. T., Martin T. J., Ng K. W. In situ hybridization to show sequential expression of osteoblast gene markers during bone formation in vivo. J Bone Miner Res. 1994 Sep;9(9):1489–1499. doi: 10.1002/jbmr.5650090922. [DOI] [PubMed] [Google Scholar]

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