Studies on vitamin D (calciferol) and its analogs. 15. 24-Nor-1.alpha.,25-dihydroxyvitamin D3 and 24-nor-25-hydroxy-5,6-trans-vitamin D3

1978 ◽  
Vol 21 (10) ◽  
pp. 1025-1029 ◽  
Author(s):  
Antonio Mourino ◽  
Patricia Blair ◽  
Wayne Wecksler ◽  
R. Lorne Johnson ◽  
Anthony W. Norman ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Dihydroxyvitamin D3

Metabolism of vitamin D in patients with primary biliary cirrhosis and alcoholic liver disease

1985 ◽  
Vol 69 (5) ◽  
pp. 561-570 ◽  
Author(s):  
E. Barbara Mawer ◽  
H. J. Klass ◽  
T. W. Warnes ◽  
Jacqueline L. Berry
Keyword(s):  
Vitamin D ◽  
Liver Disease ◽  
Primary Biliary Cirrhosis ◽  
Alcoholic Liver Disease ◽  
Vitamin D3 ◽  
Control Group ◽  
Biliary Cirrhosis ◽  
Vitamin D2 ◽  
Dihydroxyvitamin D3 ◽  
Poor Renal Function

1. The metabolism of isotopically labelled vitamin D2 and D3 has been investigated in eight patients with primary biliary cirrhosis and in five controls. The concentration of labelled vitamin D2 was lower than that of vitamin D3 in serum of patients with primary biliary cirrhosis on days 1 and 2 after intravenous injection (P < 0.005 and P < 0.05, respectively) but no difference was seen in controls. 2. Similar amounts of labelled 25-hydroxyvitamin D2 and D3 were seen in serum of the control group; the same pattern was observed in the primary biliary cirrhosis group, and no significant differences were observed between the two groups. 3. In both control and primary biliary cirrhosis groups, the serum concentration of labelled 24,25-dihydroxyvitamin D2 exceeded that of 24,25-dihydroxyvitamin D3 (significant for controls on day 2, P < 0.02) but concentrations in the two groups were not different. 4. Concentrations of labelled 25,26-dihydroxyvitamin D3 were significantly higher than those of 25,26-dihydroxyvitamin D2 in the primary biliary cirrhosis group at all times and in the control group on days 2 and 3. Both 25,26-dihydroxyvitamin D2 and D3 were higher in the serum of patients with primary biliary cirrhosis than in controls (significant on day 1, P < 0.05). 5. Urinary excretion over days 0–3 of radioactivity from both vitamins D2 and D3 was significantly higher in the primary biliary cirrhosis group than in controls: 12.03 vs 1.80% for vitamin D2 and 8.98 vs 1.76% for vitamin D3(P < 0.005). Vitamin D2-derived urinary radioactivity in primary biliary cirrhosis correlated strongly with serum bilirubin (P = 0.005). 6. The metabolism of labelled vitamin D3 was studied in seven patients with alcoholic liver disease, three of whom showed low serum concentrations of labelled 25-hydroxyvitamin D3 suggesting impaired hepatic synthesis. The 25-hydroxylation response was quantified as the relative index of 25-hydroxylation and was significantly related to two other indices of liver function. It is concluded that impaired 25-hydroxylation of vitamin D may occur in alcoholic liver disease and results from hepatocellular dysfunction. 7. Less than the predicted amounts of 1,25-dihydroxyvitamin D3 were produced in four of the seven patients with alcoholic liver disease; this defect may be attributable in part to decreased precursor 25-hydroxyvitamin D and to poor renal function.

Intestinal absorption of calcium: role of dietary phosphate and vitamin D

1981 ◽  
Vol 241 (1) ◽  
pp. G49-G53
Author(s):  
N. Brautbar ◽  
B. S. Levine ◽  
M. W. Walling ◽  
J. W. Coburn
Keyword(s):  
Vitamin D ◽  
Intestinal Absorption ◽  
Vitamin D3 ◽  
Control Groups ◽  
Dihydroxyvitamin D3 ◽  
Dietary Phosphorus ◽  
P Concentration ◽  
Dietary Phosphate ◽  
Intestinal Ca Absorption

The intestinal absorption of calcium (Ca) has been shown to depend on vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and dietary phosphorus (P) concentration. This study was designed to evaluate the role of dietary P independent of vitamin D3 or 1,25(OH)2D3. Vitamin D-deficient rats were studied during dietary P restriction and were compared with control groups raised on a normal-phosphorus diet (NP). Balance studies were sued. Net intestinal Ca absorption was significantly lower with dietary P restriction compared with the NP group. This malabsorption of Ca was corrected by the administration of either D3 for 1,25(OH)2D3, despite hypophosphatemia. Everted gut sacs showed a marked reduction in the uptake of 45Ca in the duodenum, jejunum, and ileum during dietary P restriction. We concluded that dietary P concentration plays a major role in intestinal Ca absorption in the vitamin D-deficient rats. These findings suggest an effect of the low-phosphate diet on the vitamin D-dependent, Ca-transport mechanism.

ChemInform Abstract: STUDIES ON VITAMIN D (CALCIFEROL) AND ITS ANALOGS. 15. 24-NOR-1α,25-DIHYDROXYVITAMIN D3 AND 24-NOR-25-HYDROXY-5,6-TRANS-VITAMIN D3

1979 ◽  
Vol 10 (8) ◽  
Author(s):  
A. MOURINO ◽  
P. BLAIR ◽  
W. WECKSLER ◽  
R. L. JOHNSON ◽  
A. W. NORMAN ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Dihydroxyvitamin D3

The Effect of Vitamin D and Its Metabolites on Fracture Repair in Chicks

1983 ◽  
Vol 65 (4) ◽  
pp. 429-436 ◽  
Author(s):  
S. Dekel ◽  
R. Salama ◽  
S. Edelstein
Keyword(s):  
Vitamin D ◽  
Bone Formation ◽  
Vitamin D3 ◽  
Fracture Repair ◽  
Control Group ◽  
Clinical Implications ◽  
Torsional Stress ◽  
Active Vitamin ◽  
Dihydroxyvitamin D3 ◽  
24,25 Dihydroxyvitamin D3

1. One-day-old chicks were depleted of vitamin D. At 3 weeks their right tibiae, and those of a control group given vitamin D3, were fractured and pinned. After fracture the controls were kept on vitamin D3. Another group was left vitamin D-deficient. The remaining depleted chicks, divided into four groups, were given vitamin D3, 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or a combination of 24,25(OH)2D3 and 1,25(OH)2D3. 2. The callus obtained after 9 and 14 days was subjected to torsional stress. The callus of chicks given vitamin D continuously showed the greatest resistance, whereas that of vitamin D-deficient chicks showed the smallest resistance. Repletion with either vitamin D3 or its metabolites increased the strength of the callus. Repletion with the combination of 24,25(OH)2D3 and 1,25(OH)2D3 produced the most marked results, in that the callus was even stronger than that of chicks replete with vitamin D3. 3. It is concluded that 24,25(OH)2D3 is essential for bone formation in addition to the known active vitamin D metabolite 1,25(OH)2D3, and the possible clinical implications of these findings are discussed.

scholarly journals Nutrigenomics of Vitamin D

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 676 ◽  
Author(s):  
Carsten Carlberg
Keyword(s):  
Vitamin D ◽  
Human Genome ◽  
Vitamin D3 ◽  
Skin Pigmentation ◽  
Adaptive Immune System ◽  
Molecular Response ◽  
Dihydroxyvitamin D3 ◽  
Clinical Benefits ◽  
Prevention Of Osteoporosis ◽  
Endogenous Synthesis

Nutrigenomics studies how environmental factors, such as food intake and lifestyle, influence the expression of the genome. Vitamin D3 represents a master example of nutrigenomics, since via its metabolite 1α,25-dihydroxyvitamin D3, which binds with high-affinity to the vitamin D receptor, the secosteroid directly affects the epigenome and transcriptome at thousands of loci within the human genome. Vitamin D is important for both cellular metabolism and immunity, as it controls calcium homeostasis and modulates the response of the innate and adaptive immune system. At sufficient UV-B exposure, humans can synthesize vitamin D3 endogenously in their skin, but today’s lifestyle often makes the molecule a true vitamin and micronutrient that needs to be taken up by diet or supplementation with pills. The individual’s molecular response to vitamin D requires personalized supplementation with vitamin D3, in order to obtain optimized clinical benefits in the prevention of osteoporosis, sarcopenia, autoimmune diseases, and possibly different types of cancer. The importance of endogenous synthesis of vitamin D3 created an evolutionary pressure for reduced skin pigmentation, when, during the past 50,000 years, modern humans migrated from Africa towards Asia and Europe. This review will discuss different aspects of how vitamin D interacts with the human genome, focusing on nutritional epigenomics in context of immune responses. This should lead to a better understanding of the clinical benefits of vitamin D.

Stimulation of 24R,25-dihydroxyvitamin D3 synthesis by metabolites of vitamin D3

1983 ◽  
Vol 245 (4) ◽  
pp. E359-E364 ◽  
Author(s):  
G. S. Reddy ◽  
G. Jones ◽  
S. W. Kooh ◽  
D. Fraser ◽  
H. F. DeLuca
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
The Other ◽  
Hydroxyl Group ◽  
Vitamin D Metabolites ◽  
Structural Requirements ◽  
Dihydroxyvitamin D3 ◽  
Hydroxylated Metabolites ◽  
Perfusion Period ◽  
Stimulation Of

Previously we have shown that the isolated perfused kidney from vitamin D-deficient rats converts [3H]25(OH)D3 into [3H]1 alpha,25(OH)2D3. When certain vitamin D metabolites were added to perfusate the same kidney began to synthesize [3H]24R,25(OH)2D3. In this study we investigated the structural requirements of the vitamin D molecule necessary to stimulate synthesis of [3H]24R,25(OH)2D3 in a 1-hydroxylating kidney. Kidneys were perfused with tracer [3H]25(OH)D3 (450 pM) alone and in the presence of a variety of hydroxylated metabolites and fluorinated analogues of vitamin D3 at concentrations of 450 pM to 25 microM. Tracer [3H]25(OH)D3 alone resulted in synthesis of only [3H]1 alpha,25(OH)2D3 during the 6-h perfusion period. 25-Hydroxylated metabolites [25(OH)D3, 25 nM; 1 alpha,25(OH)2D3, 25 nM; 24R,25(OH)2D3, 25 nM; 24(F)2,25(OH)D3, 50 nM] stimulated [3H]24R,25(OH)2D3 production at 2 h of perfusion. On the other hand, analogues without the 25-hydroxyl group [D3; 1 alpha(OH)D3; 25(F)D3; 1 alpha(OH),25(F)D3; 1 alpha(F)D3; 1 beta(F)D3]; did not stimulate [3H]24R,25(OH)2D3 synthesis. We conclude that the 25-hydroxyl group is an essential determinant of 24-hydroxylation.

Vitamin D in Solution: Conformations of Vitamin D3, agr,25-Dihydroxyvitamin D3, and Dihydrotachysterol3

Science ◽  
1974 ◽  
Vol 186 (4167) ◽  
pp. 939-941 ◽  
Author(s):  
R. M. Wing ◽  
W. H. Okamura ◽  
M. R. Pirio ◽  
S. M. Sine ◽  
A. W. Norman
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Dihydroxyvitamin D3 ◽  
Solution Conformations

1, 25-Dihydroxyvitamin D Suppresses TNFα-Mediated NF-κB Activation in K562 and Human CD34+ Cells and Promotes Recovery of Erythroid Colony Formation in Human CD34+ Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2097-2097
Author(s):  
Michelle Levine ◽  
Jee-Yeong Jeong ◽  
Nancy Berliner ◽  
Gary J. Vanasse
Keyword(s):  
Vitamin D ◽  
Signaling Pathways ◽  
Vitamin D Deficiency ◽  
Vitamin D3 ◽  
Nuclear Translocation ◽  
K562 Cells ◽  
T Test ◽  
Dihydroxyvitamin D3 ◽  
Human Cd34 ◽  
Cd34 Cells

Abstract Abstract 2097 Anemia of inflammation (AI) has been widely associated with chronic rheumatologic, infectious, and cardiovascular disorders and comprises one-third of cases of anemia in the elderly. Although the antimicrobial peptide hepcidin is felt to be the prime regulator of AI, emerging evidence supports the premise that subsets of AI may be mediated via hepcidin-independent inflammatory pathways, such as those modulated by tumor necrosis factor alpha (TNFα), that directly suppress erythropoiesis. A better understanding of the pathophysiology of anemia subtypes is necessary if we are to develop more effective targeted, oral therapies for patients with inflammatory anemia. Our recent analysis of elderly participants in the Third National Health and Nutrition Examination Survey (NHANES III) revealed that vitamin D deficiency was strongly associated with AI in this population, with this subgroup exhibiting a rate of vitamin D deficiency nearly twice that of similarly aged non-anemic individuals. In the current study we aimed to evaluate whether vitamin D treatment may ameliorate TNFα-mediated erythroid colony suppression in humans. Human bone marrow-derived CD34+ cells from 3 healthy adults were first cultured in methylcellulose medium containing IL-3 (10ng/ml), EPO (1U/ml), SCF (50ng/ml) in the presence or absence of TNFα (25 ng/ml) and increasing doses of 1, 25-dihydroxyvitamin D3 [calcitriol, (0.01-1nM)], and erythroid burst-forming units (BFU-E) measured on day 14. The percentage of BFU-E colonies was reduced by 50% at day 14 in the presence of 25ng/ml TNFα (p < 0.01, t-test). TNFα-mediated suppression of erythropoiesis was reversed by the addition of vitamin D3 in a dose-dependent manner, with 1nM vitamin D3 resulting in a 50% recovery of BFU-E colony numbers at day 14 (p < 0.05, t-test). Vitamin D3 alone exhibited no significant effect on BFU-E formation at all concentrations tested. Based on studies showing that vitamin D receptor may serve as a negative regulator of NF-κB transcriptional activity, we next investigated whether vitamin D3 may alter TNFα-induced NF-κB activation in both K562 and human CD34+ cells. K562 cells pre-incubated with 1nM vitamin D3 for 3, 24, 48 and 72 hours were treated with 5 ng/ml TNFα for 30 minutes, and NF-κB activity in nuclear fraction was determined by an ELISA-format oligonucleotide binding assay. TNFα treatment alone markedly increased the oligonucleotide binding activity of the NF-κB p65 subunit, which was completely blocked by co-incubation with competitor oligonucleotide, confirming the assay specificity. Pre-incubation with vitamin D3 for 3 – 48 hours showed little effect on TNFα-mediated NF-κB activation, but pre-incubation for 72 hours resulted in suppression of TNFα-induced NF-κB activity by 46% (p < 0.02, t-test). Under similar conditions, human CD34+ cells pre-incubated with 1 nM vitamin D3 for 48 hours and 72 hours exhibited 38% and 84% suppression of TNFα-induced NF-κB activity, respectively (p < 0.01 for both conditions, t-test). Reduced NF-κB activity was correlated with the decreased nuclear translocation of NF-κB in K562 cells with no significant changes in IκB degradation, suggesting that vitamin D3 regulates the NF-κB nuclear translocation independent of IκB. Western analysis of whole cell lysates from both K562 and human CD34+ cells using antibodies recognizing known TNFα-associated signaling pathways revealed robust increases in phospho-p38, phospho-JNK, and phospho-ERK1/2 in response to TNFα stimulation compared with control, with no inhibition of these signaling pathways noted in response to vitamin D3 treatment at all doses tested, suggesting that vitamin D3 does not inhibit these TNFα-induced signaling cascades. Our study indicates that 1, 25-dihydroxyvitamin D3 significantly ameliorates TNFα-mediated suppression of erythroid colony development in human CD34+ cells via mechanisms that involve modulation of NF-κB signaling pathways and supports the design of future clinical trials examining whether vitamin D3 supplementation may prove to be an effective therapy for subgroups of patients with TNFα-mediated inflammatory anemia. Disclosures: No relevant conflicts of interest to declare.

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