Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Mar;80(6):1746–1750. doi: 10.1073/pnas.80.6.1746

Do tissues other than the kidney produce 1,25-dihydroxyvitamin D3 in vivo? A reexamination.

T D Shultz, J Fox, H Heath 3rd, R Kumar
PMCID: PMC393681  PMID: 6572938

Abstract

Recent experiments have shown that 1,25-dihydroxyvitamin D3-like material is produced in cultured nonrenal cells and may be present in the sera of anephric patients. We reexamined the question of whether 1,25-dihydroxyvitamin D3 can be synthesized extrarenally in the rat in vivo. To intact, sham-operated, ureter-ligated, or acutely nephrectomized vitamin D-deficient rats raised on a diet normal in calcium and phosphorus, we gave a physiologic dose of high-specific-activity 25-hydroxy-[3H]vitamin D3 (3.6-3.8 microCi; approximately equal to 25 pmol per rat). Twenty-four hours later we examined their tissues and plasma for the presence of radiolabeled 1,25-dihydroxyvitamin D3. Large amounts of radioactivity that behaved chromatographically as identical with authentic 1,25-dihydroxyvitamin D3 were present in the plasma, bone, and intestine of the intact, sham-operated, or ureter-ligated rats. However, no radioactivity eluting in a manner similar to 1,25-dihydroxyvitamin D3 was found in plasma, bone, or intestine of acutely nephrectomized rats. We conclude that, in the acutely nephrectomized living rat, 1,25-dihydroxyvitamin D3 is not present in plasma, bone, or intestine in quantities detectable by the sensitive techniques we have used. No conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 was observed during a 24-hr period after nephrectomy of vitamin D-deprived rats. This fact casts doubt upon the significance of the in vitro production of 1,25-dihydroxyvitamin D3 by nonrenal cells as an in vivo phenomenon.

Full text

PDF
1747

Selected References

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

  1. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Bouillon R., De Moor P., Baggiolini E. G., Uskokovic M. R. A radioimmunoassay for 1,25-dihydroxycholecalciferol. Clin Chem. 1980 Apr;26(5):562–567. [PubMed] [Google Scholar]
  4. Brumbaugh P. F., Haussler D. H., Bressler R., Haussler M. R. Radioreceptor assay for 1 alpha,25-dihydroxyvitamin D3. Science. 1974 Mar 15;183(4129):1089–1091. doi: 10.1126/science.183.4129.1089. [DOI] [PubMed] [Google Scholar]
  5. DeLuca H. F. The vitamin D system in the regulation of calcium and phosphorus metabolism. Nutr Rev. 1979 Jun;37(6):161–193. doi: 10.1111/j.1753-4887.1979.tb06660.x. [DOI] [PubMed] [Google Scholar]
  6. Eisman J. A., Hamstra A. J., Kream B. E., DeLuca H. F. 1,25-Dihydroxyvitamin D in biological fluids: a simplified and sensitive assay. Science. 1976 Sep 10;193(4257):1021–1023. doi: 10.1126/science.1085035. [DOI] [PubMed] [Google Scholar]
  7. Eisman J. A., Shepard R. M., DeLuca H. F. Determination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in human plasma using high-pressure liquid chromatography. Anal Biochem. 1977 May 15;80(1):298–305. doi: 10.1016/0003-2697(77)90648-0. [DOI] [PubMed] [Google Scholar]
  8. Fraser D. R., Kodicek E. Unique biosynthesis by kidney of a biological active vitamin D metabolite. Nature. 1970 Nov 21;228(5273):764–766. doi: 10.1038/228764a0. [DOI] [PubMed] [Google Scholar]
  9. Gray R. W., Weber H. P., Dominguez J. H., Lemann J., Jr The metabolism of vitamin D3 and 25-hydroxyvitamin D3 in normal and anephric humans. J Clin Endocrinol Metab. 1974 Dec;39(6):1045–1056. doi: 10.1210/jcem-39-6-1045. [DOI] [PubMed] [Google Scholar]
  10. Gray R., Boyle I., DeLuca H. F. Vitamin D metabolism: the role of kidney tissue. Science. 1971 Jun 18;172(3989):1232–1234. doi: 10.1126/science.172.3989.1232. [DOI] [PubMed] [Google Scholar]
  11. Gray T. K., Lester G. E., Lorenc R. S. Evidence for extra-renal 1 alpha-hydroxylation of 25-hydroxyvitamin D3 in pregnancy. Science. 1979 Jun 22;204(4399):1311–1313. doi: 10.1126/science.451538. [DOI] [PubMed] [Google Scholar]
  12. Gray T. K., McAdoo T., Pool D., Lester G. E., Williams M. E., Jones G. A modified radioimmunoassay for 1,25-dihydroxycholecalciferol. Clin Chem. 1981 Mar;27(3):458–463. [PubMed] [Google Scholar]
  13. 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]
  14. Kumar R., Cohen W. R., Silva P., Epstein F. H. Elevated 1,25-dihydroxyvitamin D plasma levels in normal human pregnancy and lactation. J Clin Invest. 1979 Feb;63(2):342–344. doi: 10.1172/JCI109308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kumar R., Nagubandi S., Mattox V. R., Londowski J. M. Enterohepatic physiology of 1,25-dihydroxyvitamin D3. J Clin Invest. 1980 Feb;65(2):277–284. doi: 10.1172/JCI109669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lambert P. W., DeOreo P. B., Hollis B. W., Fu I. Y., Ginsberg D. J., Roos B. A. Concurrent measurement of plasma levels of vitamin D3 and five of its metabolites in normal humans, chronic renal failure patients, and anephric subjects. J Lab Clin Med. 1981 Oct;98(4):536–548. [PubMed] [Google Scholar]
  17. Lambert P. W., Stern P. H., Avioli R. C., Brackett N. C., Turner R. T., Greene A., Fu I. Y., Bell N. H. Evidence for extrarenal production of 1 alpha ,25-dihydroxyvitamin D in man. J Clin Invest. 1982 Mar;69(3):722–725. doi: 10.1172/JCI110501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mawer E. B., Backhouse J., Lumb G. A., Stanbury S. W. Evidence for formation of 1,25-dihydroxycholecalciferol during metabolism of vitamin D in man. Nat New Biol. 1971 Aug 11;232(2):188–189. doi: 10.1038/newbio232188a0. [DOI] [PubMed] [Google Scholar]
  19. Stern P. H., Hamstra A. J., DeLuca H. F., Bell N. H. A bioassay capable of measuring 1 picogram of 1,25-dihydroxyvitamin D3. J Clin Endocrinol Metab. 1978 Jun;46(6):891–896. doi: 10.1210/jcem-46-6-891. [DOI] [PubMed] [Google Scholar]
  20. Stern P. H., Phillips T. E., Mavreas T. Bioassay of 1,25-dihydroxyvitamin D in human plasma purified by partition, alkaline extraction, and high-pressure chromatography. Anal Biochem. 1980 Feb;102(1):22–30. doi: 10.1016/0003-2697(80)90311-5. [DOI] [PubMed] [Google Scholar]
  21. Suda T., DeLuca H. F., Tanaka Y. Biological activity of 25-hydroxyergocalciferol in rats. J Nutr. 1970 Sep;100(9):1049–1052. doi: 10.1093/jn/100.9.1049. [DOI] [PubMed] [Google Scholar]
  22. Tanaka Y., Halloran B., Schnoes H. K., DeLuca H. F. In vitro production of 1,25-dihydroxyvitamin D3 by rat placental tissue. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5033–5035. doi: 10.1073/pnas.76.10.5033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Weisman Y., Vargas A., Duckett G., Reiter E., Root A. W. Synthesis of 1,25-dihydroxyvitamin D in the nephrectomized pregnant rat. Endocrinology. 1978 Dec;103(6):1992–1996. doi: 10.1210/endo-103-6-1992. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES