scholarly journals Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

2016 ◽  
Vol 96 (1) ◽  
pp. 365-408 ◽  
Author(s):  
Sylvia Christakos ◽  
Puneet Dhawan ◽  
Annemieke Verstuyf ◽  
Lieve Verlinden ◽  
Geert Carmeliet
Keyword(s):  
Vitamin D ◽  
Cancer Progression ◽  
Dna Sequences ◽  
Critical Role ◽  
Active Form ◽  
Physiological Role ◽  
Vitamin D Metabolism ◽  
Technological Advances ◽  
Hydrogen Deuterium ◽  
Direct Binding

1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease.

scholarly journals Vitamin D: Nutrient, Hormone, and Immunomodulator

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1656 ◽  
Author(s):  
Francesca Sassi ◽  
Cristina Tamone ◽  
Patrizia D’Amelio
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Immune Cells ◽  
Critical Role ◽  
Active Form ◽  
Experimental Studies ◽  
Vitamin D Metabolism ◽  
Classical Action ◽  
Calcium Phosphorus ◽  
Specific Alteration

The classical functions of vitamin D are to regulate calcium-phosphorus homeostasis and control bone metabolism. However, vitamin D deficiency has been reported in several chronic conditions associated with increased inflammation and deregulation of the immune system, such as diabetes, asthma, and rheumatoid arthritis. These observations, together with experimental studies, suggest a critical role for vitamin D in the modulation of immune function. This leads to the hypothesis of a disease-specific alteration of vitamin D metabolism and reinforces the role of vitamin D in maintaining a healthy immune system. Two key observations validate this important non-classical action of vitamin D: first, vitamin D receptor (VDR) is expressed by the majority of immune cells, including B and T lymphocytes, monocytes, macrophages, and dendritic cells; second, there is an active vitamin D metabolism by immune cells that is able to locally convert 25(OH)D3 into 1,25(OH)2D3, its active form. Vitamin D and VDR signaling together have a suppressive role on autoimmunity and an anti-inflammatory effect, promoting dendritic cell and regulatory T-cell differentiation and reducing T helper Th 17 cell response and inflammatory cytokines secretion. This review summarizes experimental data and clinical observations on the potential immunomodulating properties of vitamin D.

scholarly journals Problems in differential diagnosis of secondary hyperparathyroidism

2021 ◽  
Vol 38 (1) ◽  
pp. 161-167
Author(s):  
S. G. Shulkina ◽  
D. O. Sirin ◽  
E. N. Smirnova ◽  
V. G. Zhelobov ◽  
N. Yu. Kolomeets ◽  
...  
Keyword(s):  
Vitamin D ◽  
Differential Diagnosis ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Vitamin D Deficiency ◽  
Clinical Case ◽  
Kidney Diseases ◽  
Active Form ◽  
Renal Tubules ◽  
Vitamin D Metabolism

Hyperparathyroidism is an endocrine disease characterized by excessive production of parathyroid hormone in the main cells of the parathyroid glands. Depending on the cause of this disease, there are primary, secondary (SHPT) and tertiary hyperparathyroidism. The most common causes of SHPT are vitamin D deficiency and chronic kidney disease (CKD). Vitamin D is converted to its active form by hydroxylation in the renal tubules. Developmental abnormalities and chronic kidney diseases lead to atrophy of the tubular epithelial cells that causes a violation of vitamin D metabolism and the development of SHPT, which in turn are accompanied by a violation of calcium-phosphorus metabolism and a syndrome of musculoskeletal disorders. This article presents an analysis of a clinical case of a patient diagnosed secondary hyperparathyroidism against the background of vitamin D deficiency combined with polycystic kidney disease. This clinical case reflects the complexity of the differential diagnosis of the disease and the tactics of patient's management.

scholarly journals Vitamin D and prostate cancer

2013 ◽  
Vol 66 (5-6) ◽  
pp. 259-262
Author(s):  
Goran Marusic ◽  
Dimitrije Jeremic ◽  
Sasa Vojinov ◽  
Natasa Filipovic ◽  
Milan Popov
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Physiological Role ◽  
In Vivo Studies ◽  
Vitamin D Metabolism ◽  
Genetic Changes ◽  
Metabolic Role

In addition to the metabolic role of vitamin D, which is well known and clearly defined, there have been many hypotheses regarding its anti-proliferative and pro-apoptotic role. Epidemiology and Significance of Prostate Cancer. Prostate cancer is the second most common malignancy in men. Long period of cancerogenesis, available tumor markers and high incidence make this cancer ideal for preventive measures. Physiological Role of Vitamin D and its Effect on Prostate Cancer Cells. In vitro and in vivo studies have shown the anti-proliferative and pro-apoptopic role of vitamin D. Disorders of vitamin D metabolism are noted in vitamin D gene level, vitamin D receptor, vitamin D responsive elements and androgen receptors. We present the most important effect of those changes on vitamin D metabolism. Conclusion. Available studies on vitamin D level in serum, prostate tissue, observed activity of vitamin D enzymes and genetic changes give us only a slight insight into the basic mechanisms of vitamin D action in the development of prostate cancer; therefore, further investigations are needed.

REMISSION OF HYPOPARATHYROIDISM DURING LACTATION: EVIDENCE FOR A PHYSIOLOGICAL ROLE FOR PROLACTIN IN THE REGULATION OF VITAMIN D METABOLISM

1987 ◽  
Vol 26 (6) ◽  
pp. 667-674 ◽  
Author(s):  
T. CUNDY ◽  
S. A. HAINING ◽  
D. F. GUILLAND-CUMMING ◽  
J. BUTLER ◽  
J. A. KANIS
Keyword(s):  
Vitamin D ◽  
Physiological Role ◽  
Vitamin D Metabolism

Assessment of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D3 concentrations in male and female multiple sclerosis patients and control volunteers

2007 ◽  
Vol 13 (5) ◽  
pp. 670-672 ◽  
Author(s):  
M.S. Barnes ◽  
M.P. Bonham ◽  
P.J. Robson ◽  
J.J. Strain ◽  
A.S. Lowe-Strong ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Active Form ◽  
Plasma Concentrations ◽  
Secondary Analysis ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Multiple Sclerosis Patients ◽  
And Control

Populations with insufficient ultraviolet exposure and who consume diets low in vitamin D have low vitamin D status (plasma 25-hydroxyvitamin D (25(OH)D) concentrations) and a reported higher incidence of multiple sclerosis (MS). The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is an effective anti-inflammatory molecule. No research to date has assessed 1,25(OH)2D3 concentrations in individuals with MS. In this study, plasma concentrations of 25(OH)D, 1,25(OH)2D 3 and parathyroid hormone (PTH) were measured in 29 individuals with MS and 22 age- and sex-matched control volunteers. There were no significant differences in plasma PTH, 25(OH)D and 1,25(OH)2D3 concentrations between individuals with MS and control volunteers. Women with MS had significantly higher 25(OH)D and 1,25(OH)2D3 concentrations than men with MS (79.1 ±45.4 versus 50.2±15.3 nmol/L, P=0.019 and 103.8± 36.8 versus 70.4±28.7 pmol/L, P=0.019, respectively). There was a significant positive correlation between 25(OH)D and 1,25(OH)2D 3 concentrations in all subjects (r=0.564, P=0.000), but secondary analysis revealed that the correlation was driven by women with MS (r=0.677, P= 0.001). Significant sex differences in vitamin D metabolism were observed and were most marked in individuals with MS, suggesting that vitamin D requirements may differ between the sexes, as well as by underlying disease state. Multiple Sclerosis 2007; 13: 670-672. http://msj.sagepub.com

scholarly journals Vitamin D as a regulator of steroidogenic enzymes

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 155 ◽  
Author(s):  
Johan Lundqvist
Keyword(s):  
Vitamin D ◽  
Steroid Hormones ◽  
Sex Hormones ◽  
Active Form ◽  
Animal Experiments ◽  
Physiological Role ◽  
Steroidogenic Enzymes ◽  
Adrenal Steroid ◽  
Wide Range ◽  
Sexual Characteristics

During the last decades, the outlook on vitamin D has widened, from being a vitamin solely involved in bone metabolism and calcium homeostasis, to being a multifunctional hormone known to affect a broad range of physiological processes. The aim of this review is to summarize the research on vitamin D as a regulator of steroidogenic enzymes. Steroid hormones exert a wide range of physiological responses, including functions in the immune system, protein and carbohydrate metabolism, water and salt balance, reproductive system and development of sexual characteristics. The balance of sex hormones is also of importance in the context of breast and prostate cancer. Steroid hormones are synthesized in steroidogenic tissues such as the adrenal cortex, breast, ovaries, prostate and testis, either from cholesterol or from steroidogenic precursors secreted from other steroidogenic tissues. The hormonally active form of vitamin D has been reported to act as a regulator of a number of enzymes involved in the regulation of steroid hormon production, and thereby the production of both adrenal steroid hormones and sex hormones. The research reviewed in the article has in large part been performed in cell culture based experiments and laboratory animal experiments, and the physiological role of the vitamin D mediated regulation of steroidogenic enzyme need to be further investigated.

scholarly journals Immune Response: A Missed Opportunity Between Vitamin D and Radiotherapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Xinyue Yu ◽  
Baocai Liu ◽  
Ning Zhang ◽  
Qian Wang ◽  
Guanghui Cheng
Keyword(s):  
Vitamin D ◽  
Immune Response ◽  
Cancer Progression ◽  
Adjuvant Radiotherapy ◽  
Treatment Resistance ◽  
Vitamin D Metabolism ◽  
Therapy Efficacy ◽  
Cancer Cell Death ◽  
Radiation Induced ◽  
Missed Opportunity

Radiotherapy (RT) is a mainstay treatment in several types of cancer and acts by mediating various forms of cancer cell death, although it is still a large challenge to enhance therapy efficacy. Radiation resistance represents the main cause of cancer progression, therefore, overcoming treatment resistance is now the greatest challenge for clinicians. Increasing evidence indicates that immune response plays a role in reprogramming the radiation-induced tumor microenvironment (TME). Intriguingly, radiation-induced immunosuppression possibly overwhelms the ability of immune system to ablate tumor cells. This induces an immune equilibrium, which, we hypothesize, is an opportunity for radiosensitizers to make actions. Vitamin D has been reported to act in synergistic with RT by potentiating antiproliferative effect induced by therapeutics. Additionally, vitamin D can also regulate the TME and may even lead to immunostimulation by blocking immunosuppression following radiation. Previous reviews have focused on vitamin D metabolism and epidemiological trials, however, the synergistic effect of vitamin D and existing therapies remains unknown. This review summarizes vitamin D mediated radiosensitization, radiation immunity, and vitamin D-regulated TME, which may contribute to more successful vitamin D-adjuvant radiotherapy.

scholarly journals A review of vitamin D and its importance to the health of dairy cattle

2020 ◽  
Vol 87 (S1) ◽  
pp. 84-87
Author(s):  
Jaka Jakob Hodnik ◽  
Jožica Ježek ◽  
Jože Starič
Keyword(s):  
Vitamin D ◽  
Dairy Cattle ◽  
Active Form ◽  
Dairy Farm ◽  
Sun Exposure ◽  
Short Review ◽  
The European Union ◽  
Vitamin D Metabolism ◽  
Milk Fever ◽  
Veterinary Faculty

AbstractThis Research Reflection short review will discuss vitamin D metabolism, its role in nutrition, disease prevention, and welfare of dairy cattle, as well as its toxicity. Vitamin D is an important fat-soluble vitamin. However, some researchers regard it as a hormone due to its function in the organism. Its role is not limited just to Ca homoeostasis and bone metabolism but is also associated with immunity. In dairy cattle it is known for preventing milk fever. Cows can acquire vitamin D in many ways for example through feed, parenteral injections or through UVB irradiation from the sun or artificial lighting. The vitamin D in feed can either be plant-/ fungi- based ergocalciferol or animal-based cholecalciferol. There is currently only one registered feed vitamin D supplement for cattle in the European Union and it is cholecalciferol. Animals can also synthesize their own vitamin D when 7-dihydrocholesterol in the skin is irradiated with UVB light resulting in cholecalciferol production. Despite its importance, many cattle are deficient in vitamin D due to inadequate supplementation or insufficient sun exposure. In a study performed at the Veterinary Faculty in Slovenia 12 high producing Holstein Friesian cows at a commercial dairy farm were blood tested for vitamin D status for three succeeding months and all but one were vitamin D insufficient in all testings. The cows were not exposed to direct sunlight and the content of vitamin D3 in feed was <400 IU/kg dry matter, which is less than half of the NRC (2001) recommendation. Deficiency can also occur due to diseases affecting the gastrointestinal tract, such as paratuberculosis, which lower the absorptive capacity of the gut. Vitamin D can be toxic if cows are over-supplemented or consume large quantities of plants like Trisetum flavescens, which contain an active form of vitamin D-calcitriol or its glycosides, that are activated by digestion in the rumen.

scholarly journals The association between circulating levels of vitamin D and inflammatory markers in the first 2 years after colorectal cancer diagnosis

2020 ◽  
Vol 13 ◽  
pp. 175628482092392 ◽  
Author(s):  
Evertine Wesselink ◽  
Michiel Balvers ◽  
Martijn J. L. Bours ◽  
Johannes H. W. de Wilt ◽  
Renger F. Witkamp ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Cancer Progression ◽  
Inflammatory Markers ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Active Form ◽  
Inverse Association ◽  
Z Score ◽  
Regression Analyses

Background: Calcitriol, the active form of vitamin D, may inhibit colorectal cancer (CRC) progression, which has been mechanistically linked to an attenuation of a pro-inflammatory state. The present study investigated the associations between circulating 25 hydroxy vitamin D3 (25(OH)D3) levels and inflammatory markers (IL10, IL8, IL6, TNFα and hsCRP) in the 2 years following CRC diagnosis. Methods: Circulating 25(OH)D3 levels and inflammatory markers were assessed at diagnosis, after 6, 12 and 24 months from 798 patients with sporadic CRC participating in two prospective cohort studies. Associations between 25(OH)D3 levels and individual inflammatory markers as well as a summary inflammatory z-score were assessed at each time point by multiple linear regression analyses. To assess the association between 25(OH)D3 and inflammatory markers over the course of 2 years, linear mixed model regression analyses were conducted. Results: Higher 25(OH)D3 levels were associated with lower IL6 levels at diagnosis, at 6 months after diagnosis and over the course of 2 years (β −0.06, 95% CI −0.08 to −0.04). In addition, 25(OH)D3 levels were inversely associated with the summary inflammatory z-score at diagnosis and over the course of 2 years (β −0.17, 95% CI −0.25 to −0.08). In addition, a significant inverse association between 25(OH)D3 levels and IL10 was found over the course of 2 years. Intra-individual analyses showed an inverse association between 25(OH)D3 and IL10, IL6 and TNFα. No statistically significant associations between 25(OH)D3 and IL8 and hsCRP levels were observed. Conclusions: Serum 25(OH)D3 levels were inversely associated with the summary inflammatory z-score and in particular with IL6 in the years following CRC diagnosis. This is of potential clinical relevance as IL6 has an important role in chronic inflammation and is also suggested to stimulate cancer progression. Further observational studies should investigate whether a possible 25(OH)D3-associated reduction of inflammatory mediators influences treatment efficacy and CRC recurrence.

scholarly journals Reshaping the way we view vitamin D signalling and the role of vitamin D in health

2004 ◽  
Vol 17 (2) ◽  
pp. 241-248 ◽  
Author(s):  
James C. Fleet ◽  
Jie Hong ◽  
Zhentao Zhang
Keyword(s):  
Vitamin D ◽  
Transcriptional Activation ◽  
Mode Of Action ◽  
Uv Light ◽  
Active Form ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Molecular Mode

AbstractAlthough the biological requirement for vitamin D can be met by epidermal exposure to UV light, there are a number of conditions where this production does not occur or is not sufficient to meet biological needs. When this happens, vitamin D must be consumed and is a nutrient. However, two distinct observations have caused researchers to rethink certain dogma in vitamin D biology. First, it appears that in addition to the hormonally active form of 1,25 dihydroxyvitamin D (1,25(OH)2D), circulating levels of 25 hydroxyvitamin D have a critical importance for optimal human health. This and other data suggest that extra-renal production of 1,25(OH)2D contributes to Ca homeostasis and cancer prevention. Second, in addition to its role in the transcriptional activation of genes through the vitamin D receptor there is now compelling evidence that 1,25(OH)2D has a second molecular mode of action; the rapid activation of second-messenger and kinase pathways. The purpose of this second mode of action is only now being explored. The present review will discuss how these two areas are reshaping our understanding of vitamin D metabolism and action.

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