Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice
Open accessAbstract
The vitamin D endocrine system is essential for calcium and bone homeostasis. The precise mode of action and the full spectrum of activities of the vitamin D hormone, 1,25-dihydroxyvitamin D [1,25-(OH)2D], can now be better evaluated by critical analysis of mice with engineered deletion of the vitamin D receptor (VDR). Absence of a functional VDR or the key activating enzyme, 25-OHD-1α-hydroxylase (CYP27B1), in mice creates a bone and growth plate phenotype that mimics humans with the same congenital disease or severe vitamin D deficiency. The intestine is the key target for the VDR because high calcium intake, or selective VDR rescue in the intestine, restores a normal bone and growth plate phenotype. The VDR is nearly ubiquitously expressed, and almost all cells respond to 1,25-(OH)2D exposure; about 3% of the mouse or human genome is regulated, directly and/or indirectly, by the vitamin D endocrine system, suggesting a more widespread function. VDR-deficient mice, but not vitamin D- or 1α-hydroxylase-deficient mice, and man develop total alopecia, indicating that the function of the VDR and its ligand is not fully overlapping. The immune system of VDR- or vitamin D-deficient mice is grossly normal but shows increased sensitivity to autoimmune diseases such as inflammatory bowel disease or type 1 diabetes after exposure to predisposing factors. VDR-deficient mice do not have a spontaneous increase in cancer but are more prone to oncogene- or chemocarcinogen-induced tumors. They also develop high renin hypertension, cardiac hypertrophy, and increased thrombogenicity. Vitamin D deficiency in humans is associated with increased prevalence of diseases, as predicted by the VDR null phenotype. Prospective vitamin D supplementation studies with multiple noncalcemic endpoints are needed to define the benefits of an optimal vitamin D status.
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There is a positive correlation between levels of vitamin D and testosterone levels.
“The study authors conclude that their results support the results of several previous works, which exhibit a positive correlation between levels of vitamin D and testosterone levels [39,40].”
From Influence of Sunlight and Oral D3 Supplementation on Serum 25(OH)D Concentration and Exercise Performance in Elite Soccer Players (2020) · cites this paper as [39]
Results of studies in genetically modified mice without vitamin D receptor show gonadal failure leading to hyper-gonadotrophic hypogonadism and reduced sperm count and motility.
“this hypothesis was supported by the results of studies in genetically modified mice, which have no receptor for vitamin D and have suffered gonadal failure leading to hyper-gonadotrophic hypogonadism as well as reduced sperm count and motility.”
From Influence of Sunlight and Oral D3 Supplementation on Serum 25(OH)D Concentration and Exercise Performance in Elite Soccer Players (2020) · cites this paper as [39]
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- Authors
- Bouillon, R., Carmeliet, G., Verlinden, L., van Etten, E., Verstuyf, A., Luderer, H. F., Lieben, L., Mathieu, C., & Demay, M.
- Affiliations
- KU Leuven (BE)
- Katholieke Universiteit Leuven, Laboratory of Experimental Medicine and Endocrinology (R.B., G.C., L.V., E.v.E., A.V., L.L., C.M.), 3000 Leuven, Belgium
- Massachusetts General Hospital (US)
- ORCID
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2008-10-01
- Volume
- 29
- Issue
- 6
- Pages
- 726-776
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- PMC
- PMC2583388
- OpenAlex
- W2038177382
- Cited by
- 1,783
- References
- 11
- Citations by year
- 2026: 37 · 2025: 78 · 2024: 78 · 2023: 108 · 2022: 78 · 2021: 102 · 2020: 103 · 2019: 108 · 2018: 121 · 2017: 131 · 2016: 107 · 2015: 107 · 2014: 107 · 2013: 137 · 2012: 132
- FWCI
- 9.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fonds Wetenschappelijk Onderzoek (G.0649.08, 0649.08, G.0233.04)
- KU Leuven
- Vlaamse regering
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 46974, R01DK046974)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › 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 receptor, vitamin D deficiency, 1,25-dihydroxyvitamin D, CYP27B1, growth plate, intestinal calcium absorption, hair loss, autoimmune disease, inflammatory bowel disease, type 1 diabetes, cancer susceptibility, cardiac hypertrophy, thrombogenicity, vitamin D supplementation, vitamin D endocrine system
- MeSH terms
- Animals, Disease Models, Animal, Endocrine System Diseases, Endocrine System, Humans, Vitamin D, Receptors, Calcitriol, Mice, Knockout, Mice
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