Vitamin D

Feldman, David; Malloy, Peter J.; Gross, Coleman

doi:10.1016/b978-012470862-4/50010-6

Cited by 32 publications

(12 citation statements)

References 377 publications

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“…Based upon the observation that CaP mortality rates in the U.S. are inversely proportional to the geographically incident UV radiation exposure from the sun, and that UV light is essential for vitamin D synthesis in the skin, a role for vitamin D in decreasing the risk of developing CaP has been suggested. The hypothesis may also offer a potential partial explanation for the increased risk of African American men to develop CaP as a result of their darker skin pigmentation impairing endogenous vitamin D synthesis (2). Data suggesting that lower circulating levels of calcitriol are a risk factor for CaP have been presented; however, some studies do not agree on these findings (3)(4)(5)(6).…”

Section: B Historical Perspective Of Vitamin D and Prostate Cancermentioning

confidence: 57%

“…Relevant to vitamin D and the prostate, it has recently been demonstrated that polymorphisms in the vitamin D receptor (VDR) gene may contribute to the risk of CaP, although not all studies can confirm this finding (5). These are the same polymorphisms that are considered to play a small but significant role in osteoporosis risk (2). The effect of polymorphisms on CaP risk may be the result of differential activity of the variant VDR alleles in transactivation of vitamin D target genes.…”

Section: B Historical Perspective Of Vitamin D and Prostate Cancermentioning

confidence: 79%

“…The study raises for discussion the subject of the wide spectrum of actions of calcitriol in CaP and its potential therapeutic use in a number of diseases. Over the past several years, it has become clear that calcitriol exhibits antiproliferative, prodifferentiating, and immunosuppressive properties in addition to its well known actions on mineral metabolism (2). This recent recognition of calcitriol's expanded range of activities has raised the possibility that it may have utility in the treatment of a variety of malignancies, immunemediated diseases, psoriasis, and a number of other conditions, including its more classical uses to treat osteoporosis and renal osteodystrophy.…”

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confidence: 99%

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Editorial/Mini-Review: Vitamin D and Prostate Cancer

Feldman

2000

Endocrinology

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Section: B Historical Perspective Of Vitamin D and Prostate Cancermentioning

confidence: 57%

Section: B Historical Perspective Of Vitamin D and Prostate Cancermentioning

confidence: 79%

mentioning

confidence: 99%

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Editorial/Mini-Review: Vitamin D and Prostate Cancer

Feldman

2000

Endocrinology

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“…[5][6][7][8] Our interest is now extended to the A-ring and the seco-B-ring triene parts: the geometry of the A-ring is important for vitamin D to bind to the VDR, and the conjugated triene has unique structural and electronic features compared with other steroid hormones. The A-ring is known to exist as a roughly equal population of two conformations in solution, which correspond to the two chair forms of the a-(1a-OH in axial and 3b-OH in equatorial orientation) and b-conformers (1a-OH in equatorial and 3b-OH in axial position), by 1 H-NMR studies (Fig. 2).…”

mentioning

confidence: 99%

“…9) These two conformers have also been found in the crystal structures of vitamin D: D 2 (both a-and b-forms), 10) D 3 (both a-and b-forms), 11) 25-hydroxyvitamin D 3 (a-form), 12) and 1,25-(OH) 2 D 3 (bform). 13) At physiological temperature, the C(6)-C(7) bond in 1,25-(OH) 2 D 3 can rotate to yield two conformations, the 6-s-trans and 6-s-cis conformers, through which slow chemical isomerism of a [1,7]-sigmatropic hydrogen shift occurs to give 1,25-dihydroxyprevitamin D 3 (Fig. 2).…”

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confidence: 99%

Fluorinated Vitamin D Analogs to Probe the Conformation of Vitamin D in Its Receptor Complex: 19F-NMR Studies and Biological Activity.

Ohno

Shimizu

Yamada

2002

CHEMICAL & PHARMACEUTICAL BULLETIN

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The active vitamin D 3 , 1a,25-dihydroxyvitamin D 3 [1,25-(OH) 2 D 3 , 1] (Fig. 1) is a multi-functional hormone. In addition to its central action in regulating calcium and phosphorus homeostasis, 1 plays a role in controlling growth and differentiation of cells and in immuno-modulation.1) 1,25-(OH) 2 D 3 has been widely used as a potential therapeutic agent in the treatment of bone metabolic diseases and the skin disorder psoriasis. However, the use of 1 is limited because a high dose causes critical hypercalcemia. Vitamin D analogs which have a selective activity profile, such as a high cell differentiating potential with little calcemic activity, have been developed by structural modification of the parent 1,25-(OH) 2 D 3 .2) 1,25-(OH) 2 D 3 exerts most of its effects via the vitamin D receptor (VDR), which is a member of the nuclear receptor superfamily.3) Binding of 1 to VDR induces a conformational change in the ligand-binding domain (LBD). VDR binds as a heterodimer with the retinoid X receptor (RXR) 4) to vitamin D response elements (VDREs), which are located in the promoter regions of 1,25-(OH) 2 D 3 target genes. It is now clear that binding of a coactivator to this heterodimer is critical for the transactivation of target genes.To understand, on a molecular basis, the mode of action of the native hormone at the transcription level, it is essential to determine in detail the three-dimensional structure of liganded VDR and its dynamic properties in solution. 1,25-(OH) 2 D 3 can be conveniently divided into four parts with unique structural characteristics, the A-ring, the seco-B-ring, the C/D-ring, and the side chain. By our initial study on the conformation-function relationship of vitamin D employing conformationally restricted side chain analogs as tools, we have proposed a concept of the active space region of the side chain. [5][6][7][8] Our interest is now extended to the A-ring and the seco-B-ring triene parts: the geometry of the A-ring is important for vitamin D to bind to the VDR, and the conjugated triene has unique structural and electronic features compared with other steroid hormones. The A-ring is known to exist as a roughly equal population of two conformations in solution, which correspond to the two chair forms of the a-(1a-OH in axial and 3b-OH in equatorial orientation) and April 2002 Chem. Pharm. Bull. 50(4) 475-483 (2002) 475 * To whom correspondence should be addressed. D derivatives to be used for the study, 4,4-difluoro-1a a,25-dihydroxyvitamin D 3 [4,4-F 2 -1,25-(OH) 2 D 3 , 2a], and (10Z)-and (10E )-19-fluoro-1a a,25-dihydroxyvitamin D 3 [19-F-1,25-(OH) 2 D 3 , 3a, 4a]. In this paper, we examined the H-NMR studies of fluorovitamin D compounds, we determined the free energy of activation for the interconversion between the two conformations of 2a (9.9 kcal/mol) and 4a (10.8, 11.5 kcal/mol). Introduction of the 1a a-hydroxyl group raised the activation energy about 1 kcal/mol. The affinity for VDR was evaluated, and the relative potency of 2a, 3a and 4a was found to be 1%...

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Comparison of Two ELISA Methods and Mass Spectrometry for Measurement of Vitamin D-Binding Protein: Implications for the Assessment of Bioavailable Vitamin D Concentrations Across Genotypes

Denburg

Hoofnagle²,

Sayed

et al. 2016

Journal of Bone and Mineral Research

103

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Studies using vitamin D-binding protein (DBP) concentrations to estimate free and bioavailable vitamin D have increased dramatically in recent years. Combinations of two single-nucleotide polymorphisms produce three major DBP isoforms (Gc1f, Gc1s and Gc2). A recent study showed that DBP concentrations quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) did not differ by race, while a widely used monoclonal ELISA quantified DBP differentially by isoform, yielding significantly lower DBP concentrations in black versus white individuals. We compared measurements of serum DBP using a monoclonal ELISA, a polyclonal ELISA, and LC-MS/MS in 125 participants in the Chronic Renal Insufficiency Cohort. Serum free and bioavailable 25OHD were calculated based on DBP concentrations from these three assays in homozygous participants, and race differences were compared. We confirmed that the monoclonal ELISA quantifies DBP differentially by isoform and demonstrated that the polyclonal ELISA is not subject to this bias. While ≤9% of the variability in DBP concentrations quantified using either LC-MS/MS or the polyclonal ELISA was explained by genotype, 85% of the variability in the monoclonal ELISA-based measures was explained by genotypes. DBP concentrations measured by the monoclonal ELISA were disproportionately lower than LC-MS/MS-based results for Gc1f homozygotes [median difference −67%; interquartile range (IQR) −71%, −64%], 95% of whom were black. In contrast, the polyclonal ELISA yielded consistently and similarly higher measurements of DBP than LC-MS/MS, irrespective of genotype, with a median percent difference of +50% [IQR +33%, +65%]. Contrary to findings using the monoclonal ELISA, DBP concentrations did not differ by race, and free and bioavailable 25OHD were significantly lower in black versus white participants based on both the polyclonal ELISA and LC-MS/MS, consistent with their lower total 25OHD. Future studies of DBP and free or bioavailable vitamin D metabolites should employ DBP assays that are not biased by DBP genotype.

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Vitamin D

Cited by 32 publications

References 377 publications

Editorial/Mini-Review: Vitamin D and Prostate Cancer

Editorial/Mini-Review: Vitamin D and Prostate Cancer

Fluorinated Vitamin D Analogs to Probe the Conformation of Vitamin D in Its Receptor Complex: 19F-NMR Studies and Biological Activity.

Comparison of Two ELISA Methods and Mass Spectrometry for Measurement of Vitamin D-Binding Protein: Implications for the Assessment of Bioavailable Vitamin D Concentrations Across Genotypes

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