Serum Protein Binding of 1,25-Dihydroxyvitamin D: A Reevaluation by Direct Measurement of Free Metabolite Levels*

Bikle, Daniel; Siiteri, Pentti K.; Ryzen, Elisabeth; Haddad, John G.; Gee, Elaine

doi:10.1210/jcem-61-5-969

Cited by 238 publications

(186 citation statements)

References 18 publications

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“…At first sight, this seems incomprehensible, because under normal circumstances at least 85% of all 1,25(OH) 2 D is bound to DBP (29). However, this phenomenon could be explained by the continuous loss of albumin-bound 1,25(OH) 2 D in the urine.…”

Section: Discussionmentioning

confidence: 99%

Relationship between free and total 1,25-dihydroxyvitamin D in conditions of modified binding

Hoof¹,

Sévaux

Baelen

et al. 2001

European Journal of Endocrinology

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Objective: A novel assay was employed to study the free 1,25-dihydroxyvitamin D (1,25(OH) 2 D) concentrations in various populations with different levels of 1,25(OH) 2 D and vitamin D binding protein (DBP). Design: In 12 healthy women before and after 3 months of oral estrogen/progestagen treatment, 10 pregnant women, and 16 patients with a nephrotic syndrome and normal renal function, the concentrations of total and free 1,25(OH) 2 D, DBP and albumin were assessed. Methods: The total concentration of 1,25(OH) 2 D in serum was assessed using a radioreceptor assay. The free fraction of 1,25(OH) 2 D was measured using symmetric dialysis. DBP was assessed using single radial immunodiffusion. Serum albumin concentrations were measured on an automated analyzer. Results: In healthy women, the concentrations of total 1,25(OH) 2 D, free 1,25(OH) 2 D and DBP were 132^19 pmolalY 92^30 fmolal and 5X59^0X43 mmolalX After 3 months of estrogen/progestagen treatment, total 1,25(OH) 2 D and DBP levels rose significantly to 175^51 pmolal and 8X321 X59 mmolal P # 0X05 and P # 0X001; the free 1,25(OH) 2 D remained unchanged 1053 9 fmolal; not significant). Pregnant women had significantly higher levels of total 1,25(OH) 2 D and DBP 239^68 pmolal and 11X32^1X77 mmolal; both P # 0X001; the free 1,25(OH) 2 D level, however, was not different 104^27 fmolal; not significant). Unexpectedly, in patients with nephrotic syndrome, no lower DBP levels were found 5X36^0X84 mmolal relative to that in controls. Despite this, levels of both total 69^26 pmolalY P # 0X001 and free 1,25(OH) 2 D 532 8 fmolal; P # 0X001 were significantly lower than in controls. Albumin levels were lowered from 628^38 mmolal to 300^84 mmolal (P # 0.001). Conclusions: Higher estrogen levels result in higher DBP levels, with a parallel rise in total 1,25(OH) 2 D levels but without a change in the biologically active free fraction. The results in patients with nephrotic syndrome show that, with increasing glomerular protein leakage, the free 1,25(OH) 2 D concentration cannot be maintained.

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Section: Discussionmentioning

confidence: 99%

Relationship between free and total 1,25-dihydroxyvitamin D in conditions of modified binding

Hoof¹,

Sévaux

Baelen

et al. 2001

European Journal of Endocrinology

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“…Only a small amount is freely available (0.4%) (59 ). There is increasing interest in the measurement of free, non-proteinbound vitamin D metabolites, because they may better reflect the true vitamin D status in humans.…”

Section: Non-protein-bound Vitamin D Speciesmentioning

confidence: 99%

Mass Spectrometric Profiling of Vitamin D Metabolites beyond 25-Hydroxyvitamin D

Müller

Volmer

2015

Clinical Chemistry

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BACKGROUND:The frequency of measurements of vitamin D in the human population has significantly increased over the last decade because vitamin D has now been linked to many diseases, in addition to its established role in bone health. Usually, serum 25-hydroxyvitamin D concentrations are measured to assess the vitamin D status of individuals. Unfortunately, many studies investigating links between vitamin D and disease also use only this single metabolite. Intricate correlations with other vitamin D metabolites or dynamic effects of downstream metabolites may therefore be overlooked. Fortunately, powerful LC-MS/MS approaches have recently become available that can simultaneously quantify the concentrations of multiple vitamin D metabolites. These approaches are challenging, however, because of inherent instrumental problems with detection of vitamin D compounds and the low concentrations of the metabolites in biological fluids.CONTENT: This review summarizes recent mass spectrometry assays for the quantitative measurement of multiple vitamin D metabolites and their application in clinical research, with a particular focus on the lowabundance downstream metabolic species generated after the initial hydroxylation to 25-hydroxyvitamin D.

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“…Specifically, the review focuses on how the analysis of the changes in vitamin D function, which have accompanied alterations in environmental exposure to u.v. light, has helped to identify new biological targets and modes of action for vitamin D. (Bikle et al 1985(Bikle et al , 1986. The vast majority of vitamin D ligands are bound to DBP but, because of its relative abundance (650 mM compared with 5 mM for DBP), some vitamin D metabolites are also carried by albumin.…”

Section: Introductionmentioning

confidence: 99%

Back to the future: a new look at ‘old’ vitamin D

Chun¹,

Adams²,

Hewison³

2008

Journal of Endocrinology

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Our perception of the vitamin D system continues to evolve. Recent studies have re-evaluated the parameters for adequate vitamin D status in humans, revealing a high prevalence of insufficiency in many populations throughout the world. Other reports have highlighted the potential consequences of vitamin D insufficiency beyond established effects on bone homeostasis. Most notably, there is now strong evidence of a role for vitamin D in modulating innate and adaptive immunities, with insufficiency being linked to infectious disease and other immune disorders. To date, signaling pathways for these new responses to vitamin D have been based on established endocrine models for active 1,25-dihydroxyvitamin D, despite present evidence for more localized, intracrine modes of action. In the following review, we provide a fresh perspective on vitamin D signaling in nonclassical target cells such as macrophages by highlighting novel factors associated with the transport and action of this pluripotent secosteroid.

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Serum Protein Binding of 1,25-Dihydroxyvitamin D: A Reevaluation by Direct Measurement of Free Metabolite Levels*

Cited by 238 publications

References 18 publications

Relationship between free and total 1,25-dihydroxyvitamin D in conditions of modified binding

Relationship between free and total 1,25-dihydroxyvitamin D in conditions of modified binding

Mass Spectrometric Profiling of Vitamin D Metabolites beyond 25-Hydroxyvitamin D

Back to the future: a new look at ‘old’ vitamin D

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