Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1972 Nov;51(11):2900–2906. doi: 10.1172/JCI107114

Metabolism of 1,25-dihydroxycholecalciferol in the rat

Charles A Frolik 1, Hector F DeLuga 1
PMCID: PMC292440  PMID: 4342957

Abstract

Administration of 60 pmoles of 1,25-dihydroxycholecalciferol to vitamin D-deficient rats on a low calcium diet gives a maximal intestinal calcium transport response in 7 hr and a maximal bone calcium mobilization response in 12 hr. During the 48 hr after injection of radioactive 1,25-dihydroxycholecalciferol, unchanged 1,25-dihydroxycholecalciferol accounts for 71-98% of the radioactivity found in the intestine with minor amounts appearing in more polar metabolites. In the bone, for the 1st 12 hr, 1,25-dihydroxycholecalciferol is the major form (75-82%) present while at 24 hr, the amount of 1,25-dihydroxycholecalciferol decreases with a corresponding rise in the amounts of metabolites both less polar and more polar than the 1,25-dihydroxycholecalciferol. Since these metabolies are at their highest concentration when bone calcium mobilization is decreasing, they are most likely not responsible for the calcium mobilization observed during the 1st 12 hr. The appearance of water-soluble radioactivity in the kidney, plasma, liver, and muscle 24 hr after 1,25-dihydroxycholecalciferol injection has been demonstrated. The present results suggest that, although 1,25-dihydroxycholecalciferol is converted to further metabolites in the rat, it is probably the form of vitamin D responsible for initiating intestinal calcium transport and bone calcium mobilization.

Full text

PDF

Selected References

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

  1. Blunt J. W., DeLuca H. F., Schnoes H. K. 25-hydroxycholecalciferol. A biologically active metabolite of vitamin D3. Biochemistry. 1968 Oct;7(10):3317–3322. doi: 10.1021/bi00850a001. [DOI] [PubMed] [Google Scholar]
  2. Boyle I. T., Miravet L., Gray R. W., Holick M. F., Deluca H. F. The response of intestinal calcium transport to 25-hydroxy and 1,25-dihydroxy vitamin D in nephrectomized rats. Endocrinology. 1972 Mar;90(3):605–608. doi: 10.1210/endo-90-3-605. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Frolik C. A., Deluca H. F. 1,25-dihydroxycholecalciferol: the metabolite of vitamin D responsible for increased intestinal calcium transport. Arch Biochem Biophys. 1971 Nov;147(1):143–147. doi: 10.1016/0003-9861(71)90320-1. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Haussler M. R., Boyce D. W., Littledike E. T., Rasmussen H. A rapidly acting metabolite of vitamin D3. Proc Natl Acad Sci U S A. 1971 Jan;68(1):177–181. doi: 10.1073/pnas.68.1.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Holick M. F., Garabedian M., DeLuca H. F. 1,25-dihydroxycholecalciferol: metabolite of vitamin D3 active on bone in anephric rats. Science. 1972 Jun 9;176(4039):1146–1147. doi: 10.1126/science.176.4039.1146. [DOI] [PubMed] [Google Scholar]
  8. Holick M. F., Schnoes H. K., DeLuca H. F. Identification of 1,25-dihydroxycholecalciferol, a form of vitamin D3 metabolically active in the intestine. Proc Natl Acad Sci U S A. 1971 Apr;68(4):803–804. doi: 10.1073/pnas.68.4.803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Lawson D. E., Fraser D. R., Kodicek E., Morris H. R., Williams D. H. Identification of 1,25-dihydroxycholecalciferol, a new kidney hormone controlling calcium metabolism. Nature. 1971 Mar 26;230(5291):228–230. doi: 10.1038/230228a0. [DOI] [PubMed] [Google Scholar]
  11. Lund J., DeLuca H. F. Biologically active metabolite of vitamin D3 from bone, liver, and blood serum. J Lipid Res. 1966 Nov;7(6):739–744. [PubMed] [Google Scholar]
  12. Martin D. L., DeLuca H. F. Influence of sodium on calcium transport by the rat small intestine. Am J Physiol. 1969 Jun;216(6):1351–1359. doi: 10.1152/ajplegacy.1969.216.6.1351. [DOI] [PubMed] [Google Scholar]
  13. Omdahl J., Holick M., Suda T., Tanaka Y., DeLuca H. F. Biological activity of 1,25-dihydroxycholecalciferol. Biochemistry. 1971 Jul 20;10(15):2935–2940. doi: 10.1021/bi00791a022. [DOI] [PubMed] [Google Scholar]
  14. Raisz L. G., Trummel C. L., Holick M. F., DeLuca H. F. 1,25-dihydroxycholecalciferol: a potent stimulator of bone resorption in tissue culture. Science. 1972 Feb 18;175(4023):768–769. doi: 10.1126/science.175.4023.768. [DOI] [PubMed] [Google Scholar]
  15. Suda T., DeLuca H. F., Hallick R. B. Synthesis of (26,27- 3 H)-25-hydroxycholecalciferol. Anal Biochem. 1971 Sep;43(1):139–146. doi: 10.1016/0003-2697(71)90118-7. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Tanaka Y., DeLuca H. F., Omdahl J., Holick M. F. Mechanism of action of 1,25-dihydroxycholecalciferol on intestinal calcium transport. Proc Natl Acad Sci U S A. 1971 Jun;68(6):1286–1288. doi: 10.1073/pnas.68.6.1286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tanaka Y., Deluca H. F. Bone mineral mobilization activity of 1,25-dihydroxycholecalciferol, a metabolite of vitamin D. Arch Biochem Biophys. 1971 Oct;146(2):574–578. doi: 10.1016/0003-9861(71)90163-9. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES