Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)2vitamin D3: Genomic and non-genomic mechanisms

Haussler, Mark R.; Jurutka, Peter W.; Mizwicki, Mathew T.; Norman, Anthony W.

doi:10.1016/j.beem.2011.05.010

Cited by 579 publications

(505 citation statements)

References 94 publications

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“…Circulating 1,25(OH) 2 D also exerts non‐genomic effects through the binding in some tissues to membrane proteins with subsequent modification of the intra‐cellular calcium flux and stimulation of tyrosine kinases ( Figure 1). 20, 27, 28 As a result of these processes, 1,25(OH) 2 D maintains calcium and phosphate homeostasis, stimulating their intestinal absorption and bone resorption 29. To accomplish this, the 1,25(OH) 2 D‐VDR‐RXR complex binds to the vitamin D response elements in the small intestinal cells, increasing the expression of the epithelial calcium channel.…”

Section: Vitamin D Physiologymentioning

confidence: 99%

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

Molina

Carrero

Bover

et al. 2017

J cachexia sarcopenia muscle

102

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The spectrum of activity of vitamin D goes beyond calcium and bone homeostasis, and growing evidence suggests that vitamin D contributes to maintain musculoskeletal health in healthy subjects as well as in patients with chronic kidney disease (CKD), who display the combination of bone metabolism disorder, muscle wasting, and weakness. Here, we review how vitamin D represents a pathway in which bone and muscle may interact. In vitro studies have confirmed that the vitamin D receptor is present on muscle, describing the mechanisms whereby vitamin D directly affects skeletal muscle. These include genomic and non‐genomic (rapid) effects, regulating cellular differentiation and proliferation. Observational studies have shown that circulating 25‐hydroxyvitamin D levels correlate with the clinical symptoms and muscle morphological changes observed in CKD patients. Vitamin D deficiency has been linked to low bone formation rate and bone mineral density, with an increased risk of skeletal fractures. The impact of low vitamin D status on skeletal muscle may also affect muscle metabolic pathways, including its sensitivity to insulin. Although some interventional studies have shown that vitamin D may improve physical performance and protect against the development of histological and radiological signs of hyperparathyroidism, evidence is still insufficient to draw definitive conclusions.

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Section: Vitamin D Physiologymentioning

confidence: 99%

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

Molina

Carrero

Bover

et al. 2017

J cachexia sarcopenia muscle

102

View full text Add to dashboard Cite

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“…The VitD hormone elicits many of its pleiotrophic effects through classical ligand-receptor signalling and downstream modulation of gene expression or indeed through non-canonical genomic-independent mechanisms (Haussler et al 2011). The VitD receptor, VDR, was first reported in 1969 as a chromatinassociated protein (Haussler & Norman 1969).…”

Section: Canonical Vitamin D Signalling and Regulationmentioning

confidence: 99%

Molecular actions of vitamin D in reproductive cell biology

et al. 2017

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Vitamin D (VitD) is an important secosteroid and has attracted attention in several areas of research due to common VitD deficiency in the population, and its potential to regulate molecular pathways related to chronic and inflammatory diseases. VitD metabolites and the VitD receptor (VDR) influence many tissues including those of the reproductive system. VDR expression has been demonstrated in various cell types of the male reproductive tract, including spermatozoa and germ cells, and in female reproductive tissues including the ovaries, placenta and endometrium. However, the molecular role of VitD signalling and metabolism in reproductive function have not been fully established. Consequently, the aim of this work is to review current metabolic and molecular aspects of the VitD-VDR axis in reproductive medicine and to propose the direction of future research. Specifically, the influence of VitD on sperm motility, calcium handling, capacitation, acrosin reaction and lipid metabolism is examined. In addition, we will also discuss the effect of VitD on sex hormone secretion and receptor expression in primary granulosa cells, along with the impact on cytokine production in trophoblast cells. The review concludes with a discussion of the recent developments in VitD-VDR signalling specifically related to altered cellular bioenergetics, which is an emerging concept in the field of reproductive medicine.Reproduction (2017) 153 R29-R42

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“…40 VDR is also expressed in AT, 41,42 and taken together this could imply that AT is not merely an organ of VD storage, but also a target organ for 1,25(OH) 2 D, and that local metabolism of VD may occur in the AT.…”

Section: Introductionmentioning

confidence: 99%

Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss

et al. 2012

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OBJECTIVE: Low vitamin D (VD) levels are common in obesity. We hypothesized that this may be due to metabolism of VD in adipose tissue (AT). Thus, we studied (1) whether the VD-metabolizing enzymes were expressed differently in AT of lean and obese individuals and in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and (2) whether their expression was influenced by weight loss. METHODS: Samples of SAT and VAT were analyzed for expression of the vitamin-D-25-hydroxylases CYP2R1, CYP2J2, CYP27A1 and CYP3A4, the 25-vitamin-D-1a-hydroxylase CYP27B1, the catabolic vitamin-D-24-hydroxylase CYP24A1, and the vitamin D receptor, using reverse transcriptase-PCR. Moreover, plasma 25-hydroxy-vitamin D (25OHD) level was measured and related to the expression of these enzymes. Samples of SAT and VAT from 20 lean women and 20 obese women, and samples of SAT from 17 obese subjects before and after a 10% weight loss were analyzed. RESULTS: A plasma 25OHD level o50 nmol l À 1 was highly prevalent in both lean (45%) and obese (90%) women (Po0.01). Plasma 25OHD increased by 27% after weight loss in the obese individuals (Po0.05). Expression levels of the 25-hydroxylase CYP2J2 and the 1a-hydroxylase CYP27B1 were decreased by 71% (Po0.0001) and 49% (Po0.05), respectively, in SAT of the obese. CYP24A1 did not differ between lean and obese women, but the expression was increased by 79% (Po0.05) after weight loss. CONCLUSION: Obesity is characterized by a decreased expression of the 25-hydroxylase CYP2J2 and the 1a-hydroxylase CYP27B1 in SAT, whereas the catabolic CYP24A1 does not differ between lean and obese women. However, the expression of CYP24A1 is increased after weight loss. Accordingly, AT has the capacity to metabolize VD locally, and this can be dynamically altered during obesity and weight loss. INTRODUCTIONLow levels of circulating 25-hydroxy-vitamin D (25OHD) are associated with increased fat mass and body mass index, 1-5 but the underlying mechanism for this association is not fully elucidated. 6 Vitamin D (VD) is stored in adipose tissue (AT), and release of VD from AT is proposed to serve as an endogenous source of VD during the winter, when cutaneous production is low or absent in several parts of the world. 7 As low circulating levels of 25OHD are common in association with the obese state, 8 several studies have examined the effect of weight loss on circulating levels of 25OHD. However, results are inconsistent. After diet-and exercise-induced weight loss, both increased 9-11 and unaltered 12,13 circulating levels of 25OHD have been reported. Likewise, after major weight loss by bariatric surgery, both temporary 14-16 and long-term increases [16][17][18] in circulating levels of 25OHD have been reported, along with reports of no changes one year after surgery. 13,19 Taken together, these findings indicate that body weight is an important factor for circulating 25OHD levels. Several other explanations for the low levels of 25OHD in obesity have been proposed: a decreased exposure to sun light, 20 ...

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Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)2vitamin D3: Genomic and non-genomic mechanisms

Cited by 579 publications

References 94 publications

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

Molecular actions of vitamin D in reproductive cell biology

Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss

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