Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1980 Feb;65(2):277–284. doi: 10.1172/JCI109669

Enterohepatic physiology of 1,25-dihydroxyvitamin D3.

R Kumar, S Nagubandi, V R Mattox, J M Londowski
PMCID: PMC371364  PMID: 7356679

Abstract

After intravenous administration of radiolabeled 1,25-dihydroxyvitamin D3 to rats, approximately 25% of the administered radioactivity appeared in the bile within 24 h. Instillation of the biliary radioactivity into the duodena of other rats was followed by recovery of 15% of the radioactivity in newly secreted bile within 24 h. The process by which products of 1,25-dihydroxyvitamin D3 were excreted in bile was not saturable in the dose range tested (0.275-650 ng). The metabolites of 1,25-dihydroxyvitamin D3 present in bile were found to be much more polar than 1,25-dihydroxyvitamin D3 and were resolved into three fractions on high performance liquid chromatography. 60% of the radioactivity present in bile was retained selectively by DEAE-cellulose; the radioactive material could be eluted from the gel at a low pH or at high salt concentrations. When bile containing the radiolabeled metabolites was incubated at 37 degrees C and pH 5 with beta-glucuronidase, there was an increase in the amount of radioactivity comigrating with 1,25-dihydroxyvitamin D3. Treatment of the products of radiolabeled 1,25-dihydroxyvitamin D3 in bile with diazomethane, an agent which converts acids into methyl esters, transformed one of the metabolites into a less polar compound. These results demonstrate that there is a quantitatively important enterophepatic circulation of the products of 1,25-dihydroxyvitamin D3 in the rat.

Full text

PDF
277

Selected References

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

  1. Arnaud S. B., Goldsmith R. S., Lambert P. W., Go V. L. 25-Hydroxyvitamin D3: evidence of an enterohepatic circulation in man. Proc Soc Exp Biol Med. 1975 Jun;149(2):570–572. doi: 10.3181/00379727-149-38853. [DOI] [PubMed] [Google Scholar]
  2. Avioli L. V., Lee S. W., McDonald J. E., Lund J., DeLuca H. F. Metabolism of vitamin D3-3H in human subjects: distribution in blood, bile, feces, and urine. J Clin Invest. 1967 Jun;46(6):983–992. doi: 10.1172/JCI105605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bell P. A., Kodicek E. Investigations on metabolites of vitamin D in rat bile. Separation and partial identification of a major metabolite. Biochem J. 1969 Dec;115(4):663–669. doi: 10.1042/bj1150663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carlson G. L., Mattox V. R. Glucuronidation of 3 alpha-hydroxysteroids in vitro. J Steroid Biochem. 1979 Feb;10(2):161–165. doi: 10.1016/0022-4731(79)90230-9. [DOI] [PubMed] [Google Scholar]
  5. Cooper B., Eakins M. N., Slater T. F. The effect of various anaesthetic techniques on the flow rate, constituents and enzymic composition of rat bile. Biochem Pharmacol. 1976 Aug 1;25(15):1711–1718. doi: 10.1016/0006-2952(76)90403-2. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Gray R. W., Caldas A. E., Wilz D. R., Lemann J., Jr, Smith G. A., DeLuca H. F. Metabolism and excretion of 3H-1,25-(OH)2-vitamin D3 in healthy adults. J Clin Endocrinol Metab. 1978 May;46(5):756–765. doi: 10.1210/jcem-46-5-756. [DOI] [PubMed] [Google Scholar]
  8. Gray R. W., Omdahl J. L., Ghazarian J. G., DeLuca H. F. 25-Hydroxycholecalciferol-1-hydroxylase. Subcellular location and properties. J Biol Chem. 1972 Dec 10;247(23):7528–7532. [PubMed] [Google Scholar]
  9. Harnden D., Kumar R., Holick M. F., Deluca H. F. Side chain metabolism of 25-hydroxy-[26,27-14C] vitamin D3 and 1,25-dihydroxy-[26,27-14C] vitamin D3 in vivo. Science. 1976 Aug 6;193(4252):493–494. doi: 10.1126/science.941020. [DOI] [PubMed] [Google Scholar]
  10. Kumar R., DeLuca H. F. Side chain oxidation of 25-hydroxy-[26,27-14C]vitamin D3 and 1,25-dihydroxy-[26,27-14C]vitamin D3 in vivo by chickens. Biochem Biophys Res Commun. 1976 Mar 8;69(1):197–200. doi: 10.1016/s0006-291x(76)80291-4. [DOI] [PubMed] [Google Scholar]
  11. Kumar R., Harnden D., DeLuca H. F. Metabolism of 1,25-dihydroxyvitamin D3: evidence for side-chain oxidation. Biochemistry. 1976 Jun 1;15(11):2420–2423. doi: 10.1021/bi00656a027. [DOI] [PubMed] [Google Scholar]
  12. Kumar R., Schnoes H. K., DeLuca H. F. Rat intestinal 25-hydroxyvitamin D3- and 1alpha,25-dihydroxyvitamin D3-24-hydroxylase. J Biol Chem. 1978 Jun 10;253(11):3804–3809. [PubMed] [Google Scholar]

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

RESOURCES