The DOI matches its Crossref record; 134 of the 134 references it cites were found in a registry or an index.
Molecular Mechanisms of Vitamin D Action
Abstract
The hormonal metabolite of vitamin D, 1α,25-dihydroxyvitamin D(3) (1,25D), initiates biological responses via binding to the vitamin D receptor (VDR). When occupied by 1,25D, VDR interacts with the retinoid X receptor (RXR) to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1,25D. By recruiting complexes of either coactivators or corepressors, ligand-activated VDR-RXR modulates the transcription of genes encoding proteins that promulgate the traditional functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. Thus, vitamin D action in a particular cell depends upon the metabolic production or delivery of sufficient concentrations of the 1,25D ligand, expression of adequate VDR and RXR coreceptor proteins, and cell-specific programming of transcriptional responses to regulate select genes that encode proteins that function in mediating the effects of vitamin D. For example, 1,25D induces RANKL, SPP1 (osteopontin), and BGP (osteocalcin) to govern bone mineral remodeling; TRPV6, CaBP(9k), and claudin 2 to promote intestinal calcium absorption; and TRPV5, klotho, and Npt2c to regulate renal calcium and phosphate reabsorption. VDR appears to function unliganded by 1,25D in keratinocytes to drive mammalian hair cycling via regulation of genes such as CASP14, S100A8, SOSTDC1, and others affecting Wnt signaling. Finally, alternative, low-affinity, non-vitamin D VDR ligands, e.g., lithocholic acid, docosahexaenoic acid, and curcumin, have been reported. Combined alternative VDR ligand(s) and 1,25D/VDR control of gene expression may delay chronic disorders of aging such as osteoporosis, type 2 diabetes, cardiovascular disease, and cancer.
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“In summary, vitamin D is responsible for storage of calcium/phosphorus in bone and amino acids in muscle.”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [29]
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1 retracted
DNA demethylation in hormone-induced transcriptional derepression
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RetractedToll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response
Liu, P. T., Stenger, S., Li, H., Wenzel, L., Tan, B. H., Krutzik, S. R., Ochoa, M. T., Schauber, J., Wu, K., Meinken, C., et al. (2006) · Science · doi:10.1126/science.1123933 · Cited by 3,924
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Endocrine regulation of energy metabolism by the skeleton
Lee, N. K., Sowa, H., Hinoi, E., Ferron, M., Ahn, J. D., Confavreux, C., Dacquin, R., Mee, P. J., McKee, M. D., Jung, D. Y., et al. (2007) · Cell · doi:10.1016/j.cell.2007.05.047 · Cited by 2,554
Nuclear Receptors and Lipid Physiology: Opening the X-Files
Chawla, A., Repa, J. J., Evans, R. M., & Mangelsdorf, D. J. (2001) · Science · doi:10.1126/science.294.5548.1866 · Cited by 2,085
FGF-23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis
Shimada, T., Hasegawa, H., Yamazaki, Y., Muto, T., Hino, R., Takeuchi, Y., Fujita, T., Nakahara, K., Fukumoto, S., & Yamashita, T. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.0301264 · Cited by 1,883
Vitamin effects on the immune system: Vitamins A and D take centre stage
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β-Catenin Controls Hair Follicle Morphogenesis and Stem Cell Differentiation in the Skin
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Research works printed but not linked: 1
- Yamamoto Y, Memezawa A, Takagi K, Ochiai E, Shindo M, Kato S (2009) A tissue-specific function by unliganded VDR. In: Abstracts from the 14th Workshop on Vitamin D, Brugge, Belgium, October 4–8, 2009, p 66
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Sorted by citations
Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects
Christakos, S., Dhawan, P., Verstuyf, A., Verlinden, L., & Carmeliet, G. (2015) · Physiological Reviews · doi:10.1152/physrev.00014.2015 · Cited by 2,105
The role of vitamin D in reducing cancer risk and progression
Feldman, D., Krishnan, A. V., Swami, S., Giovannucci, E. L., & Feldman, B. J. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3691 · Cited by 1,351
Exploring vitamin D metabolism and function in cancer
Jeon, S., & Shin, E. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0038-9 · Cited by 581
Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment
Tebben, P. J., Singh, R. J., & Kumar, R. (2016) · Endocrine Reviews · doi:10.1210/er.2016-1070 · Cited by 443
Vitamin D and Endothelial Function
Kim, D., Meza, C., Clarke, H. E., Kim, J., & Hickner, R. C. (2020) · Nutrients · doi:10.3390/nu12020575 · Cited by 403
Metadata
- Authors
- Haussler, M. R., Whitfield, G. K., Kaneko, I., Haussler, C. A., Hsieh, D., Hsieh, J.-C., & Jurutka, P. W.
- Affiliations
- University of Arizona College of Medicine- Phoenix (US)
- University of Arizona (US)
- Corresponding author
- Haussler, Mark R.
- Venue
- Calcified Tissue International
- Published
- 2012-07-11
- Volume
- 92
- Issue
- 2
- Pages
- 77-98
- ISSN
- 0171-967X (ISSN-L)
- 1432-0827
- OpenAlex
- W2017851530
- Cited by
- 759
- References
- 132
- Citations by year
- 2026: 37 · 2025: 41 · 2024: 53 · 2023: 54 · 2022: 52 · 2021: 82 · 2020: 79 · 2019: 48 · 2018: 54 · 2017: 58 · 2016: 49 · 2015: 64 · 2014: 54 · 2013: 29 · 2012: 4
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Calcified Tissue International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Vitamin D Research Studies
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin K Research Studies
- Keywords
- vitamin D, 1,25-dihydroxyvitamin D3, vitamin D receptor, retinoid X receptor, heterodimer, transcriptional regulation, calcium homeostasis, phosphate homeostasis, intestinal calcium absorption, bone remodeling, RANKL, osteocalcin, osteopontin, renal calcium reabsorption, hair cycle, keratinocytes, Wnt signaling, lithocholic acid, docosahexaenoic acid, curcumin, osteoporosis, type 2 diabetes, cardiovascular disease, cancer
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Vitamin D, Signal Transduction, Receptors, Calcitriol
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