Abstract
1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] increases intestinal calcium absorption through events that include binding of 1,25(OH)2D3 to the intracellular vitamin D receptor. In vitro studies using mammalian cell cultures reveal an increase in vitamin D receptor content after exposure to 1,25(OH)2D3. To test the hypothesis that 1,25(OH)2D3 increases enterocyte vitamin D receptor content in vivo, male rats were fed either a normal calcium diet (NCD, 1.2% Ca) or low calcium diet (LCD, 0.002% Ca). After 21 d LCD increased serum 1,25(OH)2D3 levels (27 +/- 3 vs. 181 +/- 17 pg/ml, P less than 0.001) and increased transepithelial mucosal to serosal calcium fluxes (Jms) across duodenum (65 +/- 21 vs. 204 +/- 47 nmol/cm2.h, NCD vs. LCD, P less than 0.01) and jejunum (23 +/- 3 vs. 46 +/- 4, P less than 0.007). No change in serosal to mucosal calcium fluxes (Jsm) were observed. LCD increased 1,25(OH)2D3 receptor number threefold in duodenum (32.9 +/- 6.7 vs. 98.7 +/- 13.7 fmol 1,25(OH)2D3/mg protein) and jejunum (34.1 +/- 9.5 vs. 84.9 +/- 7.7) without a change in the receptor affinity for 1,25(OH)2D3 (Kd is 0.17 +/- 0.06 vs. 0.21 +/- 0.02 nM for NCD and LCD duodenum, respectively). Duodenal polyadenylated vitamin D receptor mRNA determined by Northern blot analysis did not increase appreciably during LCD, suggesting that upregulation in vivo may not be due primarily to increased receptor synthesis. The results of this study indicate that under physiologic conditions as during chronic dietary calcium restriction, increased intestinal vitamin D receptor content accompanies increased calcium active transport. Upregulation of the vitamin D receptor by 1,25(OH)2D3 may result primarily from posttranslational processes that decrease degradation of the receptor with increased receptor synthesis responsible for a negligible portion of the accumulation.
Full text
PDF






Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brumbaugh P. F., Haussler M. R. Specific binding of 1alpha,25-dihydroxycholecalciferol to nuclear components of chick intestine. J Biol Chem. 1975 Feb 25;250(4):1588–1594. [PubMed] [Google Scholar]
- Brumbaugh P. F., Hughes M. R., Haussler M. R. Cytoplasmic and nuclear binding components for 1alpha25-dihydroxyvitamin D3 in chick parathyroid glands. Proc Natl Acad Sci U S A. 1975 Dec;72(12):4871–4875. doi: 10.1073/pnas.72.12.4871. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen T. L., Hauschka P. V., Cabrales S., Feldman D. The effects of 1,25-dihydroxyvitamin D3 and dexamethasone on rat osteoblast-like primary cell cultures: receptor occupancy and functional expression patterns for three different bioresponses. Endocrinology. 1986 Jan;118(1):250–259. doi: 10.1210/endo-118-1-250. [DOI] [PubMed] [Google Scholar]
- Costa E. M., Feldman D. Homologous up-regulation of the 1,25 (OH)2 vitamin D3 receptor in rats. Biochem Biophys Res Commun. 1986 Jun 13;137(2):742–747. doi: 10.1016/0006-291x(86)91141-1. [DOI] [PubMed] [Google Scholar]
- Costa E. M., Feldman D. Measurement of 1,25-dihydroxyvitamin D3 receptor turnover by dense amino acid labeling: changes during receptor up-regulation by vitamin D metabolites. Endocrinology. 1987 Mar;120(3):1173–1178. doi: 10.1210/endo-120-3-1173. [DOI] [PubMed] [Google Scholar]
- Costa E. M., Hirst M. A., Feldman D. Regulation of 1,25-dihydroxyvitamin D3 receptors by vitamin D analogs in cultured mammalian cells. Endocrinology. 1985 Nov;117(5):2203–2210. doi: 10.1210/endo-117-5-2203. [DOI] [PubMed] [Google Scholar]
- Favus M. J., Coe F. L., Kathpalia S. C., Porat A., Sen P. K., Sherwood L. M. Effects of chlorothiazide on 1,25-dihydroxyvitamin D3, parathyroid hormone, and intestinal calcium absorption in the rat. Am J Physiol. 1982 Jun;242(6):G575–G581. doi: 10.1152/ajpgi.1982.242.6.G575. [DOI] [PubMed] [Google Scholar]
- Favus M. J. Factors that influence absorption and secretion of calcium in the small intestine and colon. Am J Physiol. 1985 Feb;248(2 Pt 1):G147–G157. doi: 10.1152/ajpgi.1985.248.2.G147. [DOI] [PubMed] [Google Scholar]
- Favus M. J., Kathpalia S. C., Coe F. L., Mond A. E. Effects of diet calcium and 1,25-dihydroxyvitamin D3 on colon calcium active transport. Am J Physiol. 1980 Feb;238(2):G75–G78. doi: 10.1152/ajpgi.1980.238.2.G75. [DOI] [PubMed] [Google Scholar]
- Favus M. J., Langman C. B. Evidence for calcium-dependent control of 1,25-dihydroxyvitamin D3 production by rat kidney proximal tubules. J Biol Chem. 1986 Aug 25;261(24):11224–11229. [PubMed] [Google Scholar]
- Favus M. J., Walling M. W., Kimberg D. V. Effects of 1,25-dihydroxycholecalciferol on intestinal calcium transport in cortisone-treated rats. J Clin Invest. 1973 Jul;52(7):1680–1685. doi: 10.1172/JCI107349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feldman D., Chen T., Cone C., Hirst M., Shani S., Benderli A., Hochberg Z. Vitamin D resistant rickets with alopecia: cultured skin fibroblasts exhibit defective cytoplasmic receptors and unresponsiveness to 1,25(OH)2D3. J Clin Endocrinol Metab. 1982 Nov;55(5):1020–1022. doi: 10.1210/jcem-55-5-1020. [DOI] [PubMed] [Google Scholar]
- 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]
- Field M., Fromm D., McColl I. Ion transport in rabbit ileal mucosa. I. Na and Cl fluxes and short-circuit current. Am J Physiol. 1971 May;220(5):1388–1396. doi: 10.1152/ajplegacy.1971.220.5.1388. [DOI] [PubMed] [Google Scholar]
- Haussler M. R., Manolagas S. C., Deftos L. J. Evidence for a 1,25-dihydroxyvitamin D3 receptor-like macromolecule in rat pituitary. J Biol Chem. 1980 Jun 10;255(11):5007–5010. [PubMed] [Google Scholar]
- Haussler M. R., Norman A. W. Chromosomal receptor for a vitamin D metabolite. Proc Natl Acad Sci U S A. 1969 Jan;62(1):155–162. doi: 10.1073/pnas.62.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haussler M. R. Vitamin D receptors: nature and function. Annu Rev Nutr. 1986;6:527–562. doi: 10.1146/annurev.nu.06.070186.002523. [DOI] [PubMed] [Google Scholar]
- Hunziker W., Walters M. R., Norman A. W. 1,25-dihydroxyvitamin D3 receptors. Differential quantitation of endogenously occupied and unoccupied sites. J Biol Chem. 1980 Oct 25;255(20):9534–9537. [PubMed] [Google Scholar]
- KONITZER K., BINDING H. Zur Bestimmung der Serumaldolase im klinischen Laboratorium. Z Gesamte Inn Med. 1959 Mar 1;14(5):252–255. [PubMed] [Google Scholar]
- Komm B. S., Frankel F. R., Myers J. C., Lyttle C. R. Estrogen regulation of alpha 1(I)-procollagen messenger ribonucleic acid in the rat uterus. Endocrinology. 1987 Apr;120(4):1403–1410. doi: 10.1210/endo-120-4-1403. [DOI] [PubMed] [Google Scholar]
- Komm B. S., Lyttle C. R. Steroidal regulation of rat uterine in vitro mRNA translation products. J Steroid Biochem. 1984 Nov;21(5):571–577. doi: 10.1016/0022-4731(84)90333-9. [DOI] [PubMed] [Google Scholar]
- Kream B. E., DeLuca H. F., Moriarity D. M., Kendrick N. C., Ghazarian J. G. Origin of 25-hydroxyvitamin D3 binding protein from tissue cytosol preparations. Arch Biochem Biophys. 1979 Jan;192(1):318–323. doi: 10.1016/0003-9861(79)90098-5. [DOI] [PubMed] [Google Scholar]
- Kream B. E., Yamada S., Schnoes H. K., DeLuca H. F. Specific cytosol-binding protein for 1,25-dihydroxyvitamin D3 in rat intestine. J Biol Chem. 1977 Jul 10;252(13):4501–4505. [PubMed] [Google Scholar]
- Langman C. B., Favus M. J., Bushinsky D. A., Coe F. L. Effects of dietary calcium restriction on 1,25-dihydroxyvitamin D3 net synthesis by rat proximal tubules. J Lab Clin Med. 1985 Sep;106(3):286–292. [PubMed] [Google Scholar]
- Mangelsdorf D. J., Pike J. W., Haussler M. R. Avian and mammalian receptors for 1,25-dihydroxyvitamin D3: in vitro translation to characterize size and hormone-dependent regulation. Proc Natl Acad Sci U S A. 1987 Jan;84(2):354–358. doi: 10.1073/pnas.84.2.354. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McDonnell D. P., Mangelsdorf D. J., Pike J. W., Haussler M. R., O'Malley B. W. Molecular cloning of complementary DNA encoding the avian receptor for vitamin D. Science. 1987 Mar 6;235(4793):1214–1217. doi: 10.1126/science.3029866. [DOI] [PubMed] [Google Scholar]
- Pike J. W., Haussler M. R. Purification of chicken intestinal receptor for 1,25-dihydroxyvitamin D. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5485–5489. doi: 10.1073/pnas.76.11.5485. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pike J. W. Interaction between 1,25-dihydroxyvitamin D3 receptors and intestinal nuclei. Binding to nuclear constituents in vitro. J Biol Chem. 1982 Jun 25;257(12):6766–6775. [PubMed] [Google Scholar]
- Pike J. W., Sleator N. M. Hormone-dependent phosphorylation of the 1,25-dihydroxyvitamin D3 receptor in mouse fibroblasts. Biochem Biophys Res Commun. 1985 Aug 30;131(1):378–385. doi: 10.1016/0006-291x(85)91813-3. [DOI] [PubMed] [Google Scholar]
- SCHULTZ S. G., ZALUSKY R. ION TRANSPORT IN ISOLATED RABBIT ILEUM. I. SHORT-CIRCUIT CURRENT AND NA FLUXES. J Gen Physiol. 1964 Jan;47:567–584. doi: 10.1085/jgp.47.3.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walling M. W. Intestinal Ca and phosphate transport: differential responses to vitamin D3 metabolites. Am J Physiol. 1977 Dec;233(6):E488–E494. doi: 10.1152/ajpendo.1977.233.6.E488. [DOI] [PubMed] [Google Scholar]
- Walling M. W., Rothman S. S. Apparent increase in carrier affinity for intestinal calcium transport following dietary calcium restriction. J Biol Chem. 1970 Oct 10;245(19):5007–5011. [PubMed] [Google Scholar]
- Walling M. W., Rothman S. S. Phosphate-independent, carrier-mediated active transport of calcium by rat intestine. Am J Physiol. 1969 Oct;217(4):1144–1148. doi: 10.1152/ajplegacy.1969.217.4.1144. [DOI] [PubMed] [Google Scholar]