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. 1994 Sep;35(9):1219–1225. doi: 10.1136/gut.35.9.1219

Localisation of vitamin D receptor in normal human duodenum and in patients with coeliac disease.

K W Colston 1, A G Mackay 1, C Finlayson 1, J C Wu 1, J D Maxwell 1
PMCID: PMC1375697  PMID: 7959227

Abstract

Immunocytochemistry using a specific monoclonal antibody 9A7 gamma was used to identify receptors for calcitriol (1,25 (OH)2 D3), the active metabolite of vitamin D, in sections of duodenal mucosa. Specific staining for vitamin D receptors was largely restricted to nuclei of enterocytes lining crypts in duodenal biopsy specimens from normal mucosa. Vitamin D receptors were also abundant in crypts from duodenal mucosa in coeliac disease patients with mucosal damage and villous atrophy. In contrast, alkaline phosphatase, a vitamin D regulated protein, was absent from crypts but present on brush borders of normal villi, and on surface enterocytes in coeliac disease. Oestrogen receptor could not be identified in duodenal mucosa. These findings suggest that calcium malabsorption in coeliac disease does not result from the absence of vitamin D receptors, but rather from reduction in vitamin D regulated proteins and functions essential for active calcium absorption that are located in the enterocytes of the villi.

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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. Berger U., Wilson P., McClelland R. A., Colston K., Haussler M. R., Pike J. W., Coombes R. C. Immunocytochemical detection of 1,25-dihydroxyvitamin D receptors in normal human tissues. J Clin Endocrinol Metab. 1988 Sep;67(3):607–613. doi: 10.1210/jcem-67-3-607. [DOI] [PubMed] [Google Scholar]
  3. Chan S. D., Atkins D. Distribution and properties of Ca2+-ATPase, phytase, and alkaline phosphatase in isolated enterocytes from normal and vitamin D-deficient rats. Gut. 1983 Oct;24(10):886–892. doi: 10.1136/gut.24.10.886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Civitelli R., Agnusdei D., Nardi P., Zacchei F., Avioli L. V., Gennari C. Effects of one-year treatment with estrogens on bone mass, intestinal calcium absorption, and 25-hydroxyvitamin D-1 alpha-hydroxylase reserve in postmenopausal osteoporosis. Calcif Tissue Int. 1988 Feb;42(2):77–86. doi: 10.1007/BF02556338. [DOI] [PubMed] [Google Scholar]
  5. Feldman D., McCain T. A., Hirst M. A., Chen T. L., Colston K. W. Characterization of a cytoplasmic receptor-like binder for 1 alpha, 25-dihydroxycholecalciferol in rat intestinal mucosa. J Biol Chem. 1979 Oct 25;254(20):10378–10384. [PubMed] [Google Scholar]
  6. Ferguson A., Watson W. C., Maxwell J. D., Fell G. S. Alkaline phosphatase levels in normal and diseased small bowel. Gut. 1968 Feb;9(1):96–98. doi: 10.1136/gut.9.1.96. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fraser D. R. The physiological economy of vitamin D. Lancet. 1983 Apr 30;1(8331):969–972. doi: 10.1016/s0140-6736(83)92090-1. [DOI] [PubMed] [Google Scholar]
  8. Ghijsen W. E., Van Os C. H. 1 alpha, 25-Dihydroxy-vitamin D-3 regulates ATP-dependent calcium transport in basolateral plasma membranes of rat enterocytes. Biochim Biophys Acta. 1982 Jul 14;689(1):170–172. doi: 10.1016/0005-2736(82)90202-4. [DOI] [PubMed] [Google Scholar]
  9. Goff J. P., Reinhardt T. A., Beckman M. J., Horst R. L. Contrasting effects of exogenous 1,25-dihydroxyvitamin D [1,25-(OH)2D] versus endogenous 1,25-(OH)2D, induced by dietary calcium restriction, on vitamin D receptors. Endocrinology. 1990 Feb;126(2):1031–1035. doi: 10.1210/endo-126-2-1031. [DOI] [PubMed] [Google Scholar]
  10. Greene G. L., Nolan C., Engler J. P., Jensen E. V. Monoclonal antibodies to human estrogen receptor. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5115–5119. doi: 10.1073/pnas.77.9.5115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Haddad J. G., Jr, Hahn T. J. Natural and synthetic sources of circulating 25-hydroxyvitamin D in man. Nature. 1973 Aug 24;244(5417):515–517. doi: 10.1038/244515a0. [DOI] [PubMed] [Google Scholar]
  12. Huang Y. C., Lee S., Stolz R., Gabrielides C., Pansini-Porta A., Bruns M. E., Bruns D. E., Miffin T. E., Pike J. W., Christakos S. Effect of hormones and development on the expression of the rat 1,25-dihydroxyvitamin D3 receptor gene. Comparison with calbindin gene expression. J Biol Chem. 1989 Oct 15;264(29):17454–17461. [PubMed] [Google Scholar]
  13. Kiyama H., Wu J. C., Smith M. W., Lawson E. D., Emson P. C. Developmental control over vitamin-D-induced calbindin gene expression during early differentiation of chicken jejunal enterocytes. Differentiation. 1991 Mar;46(2):69–75. doi: 10.1111/j.1432-0436.1991.tb00867.x. [DOI] [PubMed] [Google Scholar]
  14. Lowe K. E., Maiyar A. C., Norman A. W. Vitamin D-mediated gene expression. Crit Rev Eukaryot Gene Expr. 1992;2(1):65–109. [PubMed] [Google Scholar]
  15. Pike J. W., Marion S. L., Donaldson C. A., Haussler M. R. Serum and monoclonal antibodies against the chick intestinal receptor for 1,25-dihydroxyvitamin D3. Generation by a preparation enriched in a 64,000-dalton protein. J Biol Chem. 1983 Jan 25;258(2):1289–1296. [PubMed] [Google Scholar]
  16. Schoen M. S., Lindenbaum J., Roginsky M. S., Holt P. R. Significance of serum level of 25-hydroxycholecalciferol in gastrointestinal disease. Am J Dig Dis. 1978 Feb;23(2):137–142. doi: 10.1007/BF01073189. [DOI] [PubMed] [Google Scholar]
  17. Sone T., McDonnell D. P., O'Malley B. W., Pike J. W. Expression of human vitamin D receptor in Saccharomyces cerevisiae. Purification, properties, and generation of polyclonal antibodies. J Biol Chem. 1990 Dec 15;265(35):21997–22003. [PubMed] [Google Scholar]
  18. Staun M., Jarnum S. Measurement of the 10,000-molecular weight calcium-binding protein in small-intestinal biopsy specimens from patients with malabsorption syndromes. Scand J Gastroenterol. 1988 Sep;23(7):827–832. doi: 10.3109/00365528809090768. [DOI] [PubMed] [Google Scholar]
  19. Thomas M. L., Xu X., Norfleet A. M., Watson C. S. The presence of functional estrogen receptors in intestinal epithelial cells. Endocrinology. 1993 Jan;132(1):426–430. doi: 10.1210/endo.132.1.8419141. [DOI] [PubMed] [Google Scholar]
  20. Walters J. R., Howard A., Charpin M. V., Gniecko K. C., Brodin P., Thulin E., Forsén S. Stimulation of intestinal basolateral membrane calcium-pump activity by recombinant synthetic calbindin-D9k and specific mutants. Biochem Biophys Res Commun. 1990 Jul 31;170(2):603–608. doi: 10.1016/0006-291x(90)92134-l. [DOI] [PubMed] [Google Scholar]
  21. Warembourg M., Perret C., Thomasset M. Distribution of vitamin D-dependent calcium-binding protein messenger ribonucleic acid in rat placenta and duodenum. Endocrinology. 1986 Jul;119(1):176–184. doi: 10.1210/endo-119-1-176. [DOI] [PubMed] [Google Scholar]
  22. Wecksler W. R., Mason R. S., Norman A. W. Specific cytosol receptors for 1,25-dihydroxyvitamin D3 in human intestine. J Clin Endocrinol Metab. 1979 Apr;48(4):715–717. doi: 10.1210/jcem-48-4-715. [DOI] [PubMed] [Google Scholar]
  23. Wensel R. H., Rich C., Brown A. C., Volwiler W. Absorption of calcium measured by intubation and perfusion of the intact hyman small intestine. J Clin Invest. 1969 Sep;48(9):1768–1775. doi: 10.1172/JCI106143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Winborn W. B., Sheridan P. J., McGill H. C., Jr Sex steroid receptors in the stomach, liver, pancreas, and gastrointestinal tract of the baboon. Gastroenterology. 1987 Jan;92(1):23–32. doi: 10.1016/0016-5085(87)90835-3. [DOI] [PubMed] [Google Scholar]
  25. van Os C. H. Transcellular calcium transport in intestinal and renal epithelial cells. Biochim Biophys Acta. 1987 Jun 24;906(2):195–222. doi: 10.1016/0304-4157(87)90012-8. [DOI] [PubMed] [Google Scholar]

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