All-trans retinoic acid antagonizes the action of calciferol and its active metabolite, 1,25-dihydroxycholecalciferol, in rats
Open accessAbstract
An antagonistic interaction between retinol and calciferol has been established. However, the mechanism by which this antagonism occurs is unclear. One possibility is that retinol affects the metabolism of calciferol. To investigate this hypothesis, retinol- and calciferol-depleted rats were given various amounts of ergocalciferol, cholecalciferol, 1alpha,25-dihydroxycholecalciferol [1,25(OH)2D3], or 24,24-difluoro-1alpha,25-dihydroxycholecalciferol [24-F2-1,25(OH)2D3] in combination with various amounts of retinyl acetate or all-trans retinoic acid (ATRA) in a series of studies. Rats administered 1720 or 3440 microg retinyl acetate once every 3 d for 33 d in combination with 25.8 ng ergocalciferol or 25 ng cholecalciferol every 3 d had lower serum calcium and greater serum phosphorus concentrations than rats fed 0 or 11.4 mug retinyl acetate every 3 d. In addition, rats fed 400 microg ATRA/d in combination with 25.8 ng ergocalciferol every 3 d, 25 ng cholecalciferol every 3 d, 2-5 ng 1,25(OH)2D3/d, or 0.5-1 ng 24-F2-1,25(OH)2D3/d had significantly lower serum calcium and higher serum phosphorus concentrations than rats not given ATRA in the diet. Therefore, both retinyl acetate and ATRA are able to antagonize the action of ergocalciferol and cholecalciferol in vivo. Additionally, ATRA antagonizes the in vivo action of 1,25(OH)2D3 and an analog, 24-F2-1,25(OH)2D3, that cannot be 24-hydroxylated. Together, these results suggest that retinol does not antagonize the action of calciferol by altering the metabolism of calciferol or 1,25(OH)2D3, but does so by another mechanism.
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High vitamin A levels decrease calcium absorption by mediating the vitamin D-calcium response.
“and similarly, high vitamin A levels decrease calcium absorption by mediating the vitamin D-calcium response [274,275]”
From Vitamin A Update: Forms, Sources, Kinetics, Detection, Function, Deficiency, Therapeutic Use and Toxicity (2021) · cites this paper as [275]
The Discussion reports that high, nontoxic amounts of retinyl acetate inhibited vitamin D’s ability to maintain serum calcium in rats. The paper measured serum calcium, not calcium absorption, and says the mechanism of the vitamin A–vitamin D interaction remains unclear. It therefore supports an effect on the vitamin D–calcium response, but not the claimed decrease in absorption or a specific mediating mechanism. (LLM, conf=0.86)
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The RXR heterodimers and orphan receptors
Mangelsdorf, D. J., & Evans, R. M. (1995) · Cell · doi:10.1016/0092-8674(95)90200-7 · Cited by 3,133 · see citing works
Kliewer, S. A., Umesono, K., Mangelsdorf, D. J., & Evans, R. M. (1992) · Nature · doi:10.1038/355446a0 · Cited by 1,489 · see citing works
Current Understanding of the Molecular Actions of Vitamin D
Jones, G., Strugnell, S. A., & DeLuca, H. F. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.4.1193 · Cited by 1,272 · see citing works
Self-citationRetinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors
Zhang, X.-K., Hoffmann, B., Tran, P., et al. (1992) · Nature · doi:10.1038/355441a0 · Cited by 963 · see citing works
A new micromethod for the colorimetric determination of inorganic phosphate
Itaya, K., & Ui, M. (1966) · Clinica Chimica Acta · doi:10.1016/0009-8981(66)90114-8 · Cited by 829 · see citing works
Biological Activity of 25-Hydroxyergocalciferol in Rats
Suda, T., DeLuca, H. F., & Tanaka, Y. (1970) · Journal of Nutrition · doi:10.1093/jn/100.9.1049 · Cited by 358 · see citing works
Self-citationVitamin A antagonizes calcium response to vitamin D in man
Johansson, S., & Melhus, H. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.10.1899 · Cited by 176 · see citing works
Vitamin A Antagonizes the Action of Vitamin D in Rats
Rohde, C. M., Manatt, M., Clagett‐Dame, M., & DeLuca, H. F. (1999) · Journal of Nutrition · doi:10.1093/jn/129.12.2246 · Cited by 153 · see citing works
Self-citationRetinoic acid stimulates 1,25-dihydroxyvitamin D3 binding in rat osteosarcoma cells.
Petkovich, P. M., Heersche, J. N. M., Tinker, D. O., et al. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)39723-5 · Cited by 89 · see citing works
Metz, A. L., Walser, M. Μ., & Olson, W. G. (1985) · Journal of Nutrition · doi:10.1093/jn/115.7.929 · Cited by 68 · see citing works
Hypervitaminosis A and Calcium-Regulating Hormones in the Rat
Frankel, T. L., Seshadri, M. S., McDowall, D., & Cornish, C. J. (1986) · Journal of Nutrition · doi:10.1093/jn/116.4.578 · Cited by 63 · see citing works
Effects of Hypervitaminosis A and D on Skeletal Metabolism
Clark, I., & Smith, M. R. (1964) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)91422-5 · Cited by 52 · see citing works
Aburto, A., Edwards, H. M., & Britton, W. M. (1998) · Poultry Science · doi:10.1093/ps/77.4.585 · Cited by 52 · see citing works
A Highly Sensitive Method for Large-Scale Measurements of 1,25-Dihydroxyvitamin D
Arbour, N. C., Ross, T. K., Zierold, C., et al. (1998) · Analytical Biochemistry · doi:10.1006/abio.1997.2439 · Cited by 49 · see citing works
Allegretto, E. A., Shevde, N. K., Zou, A., Howell, S. R., Boehm, M. F., Hollis, B. W., & Pike, J. W. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.41.23906 · Cited by 49 · see citing works
Aburto, A., & Britton, W. M. (1998) · Poultry Science · doi:10.1093/ps/77.4.570 · Cited by 48 · see citing works
THE AMELIORATION OF HYPERVITAMINOSIS D IN RATS WITH VITAMIN A
Clark, I., & Bassett, C. A. L. (1962) · The Journal of Experimental Medicine · doi:10.1084/jem.115.1.147 · Cited by 46 · see citing works
Chen, T. L., & Feldman, D. I. (1985) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(85)90990-8 · Cited by 44 · see citing works
24,24-Difluoro-1,25-dihydroxyvitamin D3: In vitro production, isolation, and biological activity
Tanaka, Y., DeLuca, H. F., Schnoes, H. K., et al. (1980) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(80)90304-5 · Cited by 41 · see citing works
Self-citationMunder, M., Herzberg, I. M., Zierold, C., et al. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.7.2795 · Cited by 36 · see citing works
[12] Atomic absorption spectrometry
Slavin, W. (1988) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(88)58052-7 · Cited by 32 · see citing works
Metabolism of 1α,25-Dihydroxyvitamin D3in Vitamin D Receptor-Ablated Mice in Vivo
Endres, B., Kato, S., & DeLuca, H. F. (2000) · Biochemistry · doi:10.1021/bi9923757 · Cited by 28 · see citing works
Self-citationGrant, A. B. (1951) · Nature · doi:10.1038/168789b0 · Cited by 26 · see citing works
Biological activity of 24,24-difluoro-1,25-dihydroxyvitamin D3
Okamoto, S., Tanaka, Y., DeLuca, H. F., et al. (1983) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1983.244.2.e159 · Cited by 16 · see citing works
Self-citationA Factor in Hay inhibiting the Action of Vitamin D
Weits, J. (1952) · Nature · doi:10.1038/170891a0 · Cited by 15 · see citing works
The rachitogenic effect of vitamin A.
Grant, A. B., & O'hara, P. B. (1957) · New Zealand Journal of Science and Technology, Section A · Cited by 15 · see citing works
Reinhardt, T. A., Koszewski, N. J., Omdahl, J., & Horst, R. L. (1999) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1335 · Cited by 14 · see citing works
Retinol and retinoic acid modulate the metabolism of 25‐hydroxyvitamin D3 in kidney cell culture
Trechsel, U., Fleisch, H. A., & Monod, A. (1981) · FEBS Letters · doi:10.1016/0014-5793(81)80956-8 · Cited by 13 · see citing works
Tabor, F. S., Dutcher, R. A., & Guerrant, N. B. (1936) · Journal of Nutrition · doi:10.1093/jn/12.1.39 · Cited by 5 · see citing works
The Genetics and Biology of Vitamin D
DeLuca, H. F. (1997) · Principles of medical biology · doi:10.1016/s1569-2582(97)80174-2 · Cited by 3 · see citing works
Self-citationVITAMIN D ACTIVITY IN ROUGHAGES
(2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1959.tb06406.x · Cited by 2 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [20]20. Mangelsdorf, D. J., Umesono, K. & Evans, R. M. (1994) The retinoid receptors. In: The Retinoids: Biology, Chemistry, and Medicine (Sporn, M. B., Rob- erts, A. B. & Goodman, D. S., eds.), pp. 319 -349. Raven Press, New York, NY.
- [30]30. Horst, R. L. & Reinhardt, T. A. (1997) Vitamin D metabolism. In: Vitamin D (Feldman, D., Glorieux, F. H. & Pike, J. W., eds.), pp. 13-31. Academic Press, New York, NY.
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Carazo, A., Macáková, K., Matoušová, K., Krčmová, L. K., Protti, M., & Mladěnka, P. (2021) · Nutrients · doi:10.3390/nu13051703 · Cited by 418 · see citing works
- Authors
- Rohde, C. M., & DeLuca, H. F.
- Affiliations
- Pfizer (United States) (US)
- University of Wisconsin–Madison (US)
- Corresponding author
- DeLuca, Hector F.
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 135
- Issue
- 7
- Pages
- 1647-1652
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2112717101
- Cited by
- 42
- References
- 31
- Citations by year
- 2024: 1 · 2021: 2 · 2020: 3 · 2019: 1 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 7
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Keywords
- all-trans retinoic acid, calciferol, vitamin D2, vitamin D3, 1,25-dihydroxyvitamin D3, vitamin D metabolism, serum calcium, serum phosphorus, retinyl acetate
- MeSH terms
- Retinyl Esters, Animals, Calcitriol, Calcium, Diterpenes, Ergocalciferols, Male, Phosphorus, Tretinoin, Vitamin A, Rats, Sprague-Dawley, Rats
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