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. 1986 Aug;78(2):592–596. doi: 10.1172/JCI112614

Production of 1,25-dihydroxyvitamin D3 by human T cell lymphotrophic virus-I-transformed lymphocytes.

D A Fetchick, D R Bertolini, P S Sarin, S T Weintraub, G R Mundy, J F Dunn
PMCID: PMC423599  PMID: 3016032

Abstract

The human T cell lymphotrophic virus type I (HTLV-I) has recently been identified in a T cell lymphoma associated with hypercalcemia and increased bone turnover. Since increased serum concentrations of 1,25-dihydroxyvitamin D have been reported in this disease, we have examined the capacity of HTLV-I-infected cord blood lymphocytes to metabolize 25-hydroxyvitamin D3. Our results demonstrate that HTLV-I-infected cells have the capacity to metabolize 25-hydroxyvitamin D3 to a substance that co-migrates with 1,25-dihydroxyvitamin D3 by high performance liquid chromatography over a silica column using either 12% isopropanol in hexane or 5% isopropanol in dichloromethane. The metabolite binds to the 1,25-dihydroxyvitamin D3 receptor in rat osteosarcoma cells and stimulates bone resorption in cultures of fetal rat long bones. Mass spectrometric analysis of the metabolite confirmed the presence of 1,25-dihydroxyvitamin D3. Production of 1,25-dihydroxyvitamin D by lymphoma cells may contribute to the pathogenesis of the hypercalcemia seen in patients with HTLV-I-associated T cell lymphomas.

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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., Singer F. R., Gacad M. A., Sharma O. P., Hayes M. J., Vouros P., Holick M. F. Isolation and structural identification of 1,25-dihydroxyvitamin D3 produced by cultured alveolar macrophages in sarcoidosis. J Clin Endocrinol Metab. 1985 May;60(5):960–966. doi: 10.1210/jcem-60-5-960. [DOI] [PubMed] [Google Scholar]
  2. Bell N. H., Stern P. H., Pantzer E., Sinha T. K., DeLuca H. F. Evidence that increased circulating 1 alpha, 25-dihydroxyvitamin D is the probable cause for abnormal calcium metabolism in sarcoidosis. J Clin Invest. 1979 Jul;64(1):218–225. doi: 10.1172/JCI109442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Breslau N. A., McGuire J. L., Zerwekh J. E., Frenkel E. P., Pak C. Y. Hypercalcemia associated with increased serum calcitriol levels in three patients with lymphoma. Ann Intern Med. 1984 Jan;100(1):1–6. doi: 10.7326/0003-4819-100-1-1. [DOI] [PubMed] [Google Scholar]
  4. Davies M., Mawer E. B., Hayes M. E., Lumb G. A. Abnormal vitamin D metabolism in Hodgkin's lymphoma. Lancet. 1985 May 25;1(8439):1186–1188. doi: 10.1016/s0140-6736(85)92864-8. [DOI] [PubMed] [Google Scholar]
  5. Delvin E. E., Arabian A., Glorieux F. H., Mamer O. A. In vitro metabolism of 25-hydroxycholecalciferol by isolated cells from human decidua. J Clin Endocrinol Metab. 1985 May;60(5):880–885. doi: 10.1210/jcem-60-5-880. [DOI] [PubMed] [Google Scholar]
  6. Frankel T. L., Mason R. S., Hersey P., Murray E., Posen S. The synthesis of vitamin D metabolites by human melanoma cells. J Clin Endocrinol Metab. 1983 Sep;57(3):627–631. doi: 10.1210/jcem-57-3-627. [DOI] [PubMed] [Google Scholar]
  7. Grossman B., Schechter G. P., Horton J. E., Pierce L., Jaffe E., Wahl L. Hypercalcemia associated with T-cell lymphoma-leukemia. Am J Clin Pathol. 1981 Feb;75(2):149–155. doi: 10.1093/ajcp/75.2.149. [DOI] [PubMed] [Google Scholar]
  8. Holick M. F., Schnoes H. K., DeLuca H. F., Suda T., Cousins R. J. Isolation and identification of 1,25-dihydroxycholecalciferol. A metabolite of vitamin D active in intestine. Biochemistry. 1971 Jul 6;10(14):2799–2804. doi: 10.1021/bi00790a023. [DOI] [PubMed] [Google Scholar]
  9. Howard G. A., Turner R. T., Sherrard D. J., Baylink D. J. Human bone cells in culture metabolize 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3. J Biol Chem. 1981 Aug 10;256(15):7738–7740. [PubMed] [Google Scholar]
  10. Lester G. E., Horst R. L., Napoli J. L. Formation of 19-nor-10-keto-25-hydroxyvitamin D3 in cultured mammalian cells. Biochem Biophys Res Commun. 1984 May 16;120(3):919–925. doi: 10.1016/s0006-291x(84)80194-1. [DOI] [PubMed] [Google Scholar]
  11. Manolagas S. C., Culler F. L., Howard J. E., Brickman A. S., Deftos L. J. The cytoreceptor assay for 1,25-dihydroxyvitamin D and its application to clinical studies. J Clin Endocrinol Metab. 1983 Apr;56(4):751–760. doi: 10.1210/jcem-56-4-751. [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. NIH conference. Pulmonary sarcoidosis: a disease characterized and perpetuated by activated lung T-lymphocytes. Ann Intern Med. 1981 Jan;94(1):73–94. doi: 10.7326/0003-4819-94-1-73. [DOI] [PubMed] [Google Scholar]
  14. Okabe T., Ishizuka S., Fujisawa M., Watanabe J., Takaku F. Sarcoid granulomas metabolize 25-hydroxyvitamin D3 in vitro. Biochem Biophys Res Commun. 1984 Sep 17;123(2):822–830. doi: 10.1016/0006-291x(84)90304-8. [DOI] [PubMed] [Google Scholar]
  15. Popovic M., Lange-Wantzin G., Sarin P. S., Mann D., Gallo R. C. Transformation of human umbilical cord blood T cells by human T-cell leukemia/lymphoma virus. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5402–5406. doi: 10.1073/pnas.80.17.5402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Popovic M., Sarin P. S., Robert-Gurroff M., Kalyanaraman V. S., Mann D., Minowada J., Gallo R. C. Isolation and transmission of human retrovirus (human t-cell leukemia virus). Science. 1983 Feb 18;219(4586):856–859. doi: 10.1126/science.6600519. [DOI] [PubMed] [Google Scholar]
  17. Puzas J. E., Turner R. T., Forte M. D., Kenny A. D., Baylink D. J. Metabolism of 25(OH)D3 to 1,25(OH)2D3 and 24,25(OH)2D3 by chick chorioallantoic cells in culture. Gen Comp Endocrinol. 1980 Sep;42(1):116–122. doi: 10.1016/0016-6480(80)90264-6. [DOI] [PubMed] [Google Scholar]
  18. RAISZ L. G. BONE RESORPTION IN TISSUE CULTURE. FACTORS INFLUENCING THE RESPONSE TO PARATHYROID HORMONE. J Clin Invest. 1965 Jan;44:103–116. doi: 10.1172/JCI105117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reeve L., Tanaka Y., DeLuca H. F. Studies on the site of 1,25-dihydroxyvitamin D3 synthesis in vivo. J Biol Chem. 1983 Mar 25;258(6):3615–3617. [PubMed] [Google Scholar]
  20. Reinhardt T. A., Horst R. L., Orf J. W., Hollis B. W. A microassay for 1,25-dihydroxyvitamin D not requiring high performance liquid chromatography: application to clinical studies. J Clin Endocrinol Metab. 1984 Jan;58(1):91–98. doi: 10.1210/jcem-58-1-91. [DOI] [PubMed] [Google Scholar]
  21. Rosenthal N., Insogna K. L., Godsall J. W., Smaldone L., Waldron J. A., Stewart A. F. Elevations in circulating 1,25-dihydroxyvitamin D in three patients with lymphoma-associated hypercalcemia. J Clin Endocrinol Metab. 1985 Jan;60(1):29–33. doi: 10.1210/jcem-60-1-29. [DOI] [PubMed] [Google Scholar]
  22. Sarin P. S., Gallo R. C. Human T-lymphotropic retroviruses in adult T-cell leukemia-lymphoma and acquired immune deficiency syndrome. J Clin Immunol. 1984 Nov;4(6):415–423. doi: 10.1007/BF00916570. [DOI] [PubMed] [Google Scholar]
  23. Singer F. R., Powell D., Minkin C., Bethune J. E., Brickman A., Coburn J. W. Hypercalcemia in reticulum cell sarcoma without hyperparathyroidism of skeletal metastases. Ann Intern Med. 1973 Mar;78(3):365–369. doi: 10.7326/0003-4819-78-3-365. [DOI] [PubMed] [Google Scholar]
  24. Turner R. T., Puzas J. E., Forte M. D., Lester G. E., Gray T. K., Howard G. A., Baylink D. J. In vitro synthesis of 1 alpha,25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol by isolated calvarial cells. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5720–5724. doi: 10.1073/pnas.77.10.5720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Weisman Y., Harell A., Edelstein S., David M., Spirer Z., Golander A. 1 alpha, 25-Dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 in vitro synthesis by human decidua and placenta. Nature. 1979 Sep 27;281(5729):317–319. doi: 10.1038/281317a0. [DOI] [PubMed] [Google Scholar]
  26. Zaloga G. P., Eil C., Medbery C. A. Humoral hypercalcemia in Hodgkin's disease. Association with elevated 1,25-dihydroxycholecalciferol levels and subperiosteal bone resorption. Arch Intern Med. 1985 Jan;145(1):155–157. doi: 10.1001/archinte.145.1.155. [DOI] [PubMed] [Google Scholar]

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