1,25-Dihydroxyvitamin D3 downregulates the rat intestinal vitamin D3-25-hydroxylaseCYP27A

2001 ◽  
Vol 281 (2) ◽  
pp. E315-E325 ◽  
Author(s):  
Catherine Theodoropoulos ◽  
Christian Demers ◽  
Ali Mirshahi ◽  
Marielle Gascon-Barré
Keyword(s):  
Vitamin D ◽  
Direct Action ◽  
Dihydroxyvitamin D3 ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Protein Levels ◽  
25 Hydroxyvitamin D ◽  
Extrahepatic Tissues ◽  
Mrna Half Life

The vitamin D3-25-hydroxylase CYP27A is located predominantly in liver, but its expression is also detected in extrahepatic tissues. Our aim was to evaluate the regulation of CYP27A by vitamin D3 (D3) or its metabolites in rat duodena. Vitamin D-depleted rats were repleted with D3, 25-hydroxyvitamin D (25OHD), or 1,25-dihydroxyvitamin D3[1,25(OH)2D3] or acutely injected 1,25(OH)2D3 to investigate the mechanisms of action of the hormone. All D3 compounds led to a progressive decrease in CYP27A mRNA, with levels after D3 representing 20% of that observed in D depletion. 25OHD decreased CYP27A mRNA by 55%, whereas 1,25(OH)2D3 led to a 40% decrease, which was accompanied by a 31% decrease in CYP27A protein levels and an 89% decrease in enzyme activity. Peak circulating 1,25(OH)2D3 concentrations were, however, the highest in D3-repleted, followed by 25OHD- and 1,25(OH)2D3-repleted animals. 1,25(OH)2D3 resulted in a decrease in both CYP27A mRNA half-life and transcription rate. Our data illustrate that the intestine expresses the D3-25-hydroxylase and that the gene is highly regulated in vivo through a direct action of 1,25(OH)2D3 or through the local production of D3 metabolites.

scholarly journals Regulation of vitamin D-1alpha-hydroxylase and -24-hydroxylase expression by dexamethasone in mouse kidney

2000 ◽  
Vol 164 (3) ◽  
pp. 339-348 ◽  
Author(s):  
N Akeno ◽  
A Matsunuma ◽  
T Maeda ◽  
T Kawane ◽  
N Horiuchi
Keyword(s):  
Vitamin D ◽  
Enzyme Activity ◽  
Mrna Expression ◽  
Direct Action ◽  
Plasma Concentrations ◽  
Mrna Abundance ◽  
Subcutaneous Injections ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

We investigated the effects of dexamethasone on vitamin D-1alpha-hydroxylase and -24-hydroxylase expression and on vitamin D receptor (VDR) content in the kidneys of mice fed either a normal (NCD) diet or a calcium- and vitamin D-deficient (LCD) diet for 2 weeks. For the last 5 days mice received either vehicle or dexamethasone (2 mg/kg per day s.c.). Dexamethasone significantly increased plasma calcium concentrations without changing plasma concentrations of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) in both NCD and LCD groups. Northern blot and enzyme activity analyses in NCD mice revealed that dexamethasone increased renal VDR mRNA expression modestly and greatly increased 24-hydroxylase mRNA abundance and enzyme activity, but did not affect 1alpha-hydroxylase mRNA abundance and enzyme activity. In mice fed an LCD diet, dexamethasone increased renal VDR mRNA expression 1.5-fold, decreased 1alpha-hydroxylase mRNA abundance (52%) and activity (34%), and markedly increased 24-hydroxylase mRNA abundance (16-fold) and enzyme activity (9-fold). Dexamethasone treatment did not alter functional VDR number (B(max) 125-141 fmol/mg protein) or ligand affinity (K(d) 0.13-0.10 nM) in LCD mice. Subcutaneous injections of 1,25(OH)(2)D(3) (0.24 nmol/kg per day for 5 days) into NCD mice strongly increased renal 24-hydroxylase mRNA abundance and enzyme activity, while there was no effect of dexamethasone on renal 24-hydroxylase expression in these mice. This may be due to overwhelming induction of 24-hydroxylase by 1,25(OH)(2)D(3). These findings suggest that glucocorticoid-induced osteoporosis is caused by direct action of the steroids on bone, and the regulatory effect of glucocorticoids on renal 25-hydroxyvitamin D(3) metabolism may be less implicated in the initiation and progression of the disease.

Role of 25-hydroxyvitamin D3 dose in determining rat 1,25-dihydroxyvitamin D3 production

1990 ◽  
Vol 258 (5) ◽  
pp. E780-E789 ◽  
Author(s):  
R. Vieth ◽  
K. McCarten ◽  
K. H. Norwich
Keyword(s):  
Specific Activity ◽  
Metabolic Clearance ◽  
Dihydroxyvitamin D3 ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Dose Dependent

To understand the relationships among 1) the dose of 25-hydroxyvitamin D [25(OH)D] in vivo, 2) the activity of 1-hydroxylase in renal mitochondria, and 3) the production of 1,25-dihydroxyvitamin D [1,25(OH)2D] in vivo, we gave rats different chronic or acute doses of 25-hydroxyvitamin D3 [25(OH)D3]. We followed the metabolism of intracardially administered [25-hydroxy-26,27-methyl-3H]cholecalciferol [25(OH)[3H]D3] for 24 h before killing by measuring extracts of serum by chromatography. Specific activity of 1-hydroxylase in kidney was measured at death. In rats given 0-2,000 pmol 25(OH)D3 chronically by mouth, there was a dose-dependent decline in the percent of serum radioactivity made up of 1,25-dihydroxy-[26,27-methyl-3H]cholecalciferol [1,25(OH)2[3H]D3] as well as a decline in mitochondrial 1-hydroxylase, and these correlated significantly (r = 0.83, P less than 0.001). Serum %1,25(OH)2[3H]D3 in this experiment ranged from 0.8 to 42%. A small part of this range could be accounted for by a faster metabolic clearance rate (MCR) of 1,25(OH)2D3 from rats supplemented with 25(OH)D3 (MCR, 2.12 +/- 0.10 ml/min) compared with rats restricted in vitamin D (MCR, 0.94 +/- 0.06 ml/min, P less than 0.001). The activity of 1-hydroxylase was by far the major factor determining serum %1,25(OH)2[3H]D3. When different acute doses of 25(OH)D3 were given to rats with identical specific activities of 1-hydroxylase, the resulting 1,25(OH)2D3 concentrations in serum correlated with the 25(OH)D3 dose (r = 0.99, P less than 0.001). We conclude that the behavior of 1-hydroxylase in vivo is analogous to the classic behavior in vitro of an enzyme functioning below its Michaelis constant (Km). The amount of 1-hydroxylase present in renal mitochondria determines the fraction (not simply the quantity) of 25(OH)D metabolized to 1,25(OH)2D3 in vivo.

scholarly journals Changes in serum levels of 1,25-dihydroxyvitamin D3, calcium and phosphorus with age and vitamin D status in chickens

1984 ◽  
Vol 52 (2) ◽  
pp. 329-334 ◽  
Author(s):  
Saleh H. Sedrani
Keyword(s):  
Vitamin D ◽  
Serum Level ◽  
Sexual Maturity ◽  
Serum Levels ◽  
Minimal Amount ◽  
Dihydroxyvitamin D3 ◽  
Dietary Regimen ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

1. The effects of vitamin D3(D3) on serum levels of 1, 25-dihydroxyvitamin D3(1, 25(OH)2D3), ionic calcium, total Ca and phosphorus in chicks were studied from the time of hatching until sexual maturity.2. Chicks fed on a diet low in D3showed a serum level of 1, 25(OH)2D3higher than that in chicks on a normal-D3diet, for both sexes and at any given age.3. A dramatic increase in the serum level of 1, 25(OH)2D3occurred in female birds approaching sexual maturity and in laying hens raised on the low-D3diet the level was five times that of their counterparts raised on a normal-D3diet.4. Theserum 1, 25(OH)2D3levelin adultmalesin thelow-D3groups wasseven timesthatofthoseon thenormal-D3diet.5. The serum level of 25-hydroxyvitamin D3remained relatively unchanged at weeks 2 and 15 in birds on a low D3intake as well as in those fed on a normal-D3diet. Nevertheless, the levels of 25-hydroxyvitamin D3were different between the two groups.6. No significant change was observed in the level of ionized serum Ca in relation to dietary regimen, but there was an increase in total Ca concentration in females with the onset of reproduction.7. The serum P level decreased gradually with age, reaching a minimum value 3 and 8 weeks before laying commenced in the groups on low- and normal-D3diets respectively. An increase was observed when the hens began laying.8. Chicks adapted to a low-D3diet by elevation of their plasma level of 1, 25(OH)2D3. The mechanism by which this is achieved is not known, but the results suggest that parathyroid hormone, Ca and P are unlikely to play roles in the adaptive increase in the level of 1, 25(OH)2D3in the blood of chicks given a minimal amount of D3. The possibility that the rate of degradation of 1, 25(OH)2D3is greatly reduced under these conditions cannot be excluded and this could account for the level of this metabolite in those birds.

Effect of 1,25-dihydroxyvitamin D3 on rat pituitary prolactin release

1987 ◽  
Vol 116 (4) ◽  
pp. 459-464 ◽  
Author(s):  
Kid Törnquist
Keyword(s):  
Pituitary Cells ◽  
Dihydroxyvitamin D3 ◽  
Enhancing Effect ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Rat Pituitary ◽  
25 Hydroxyvitamin D ◽  
Pituitary Prolactin

Abstract. The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on PRL secretion from rat pituitary in vivo and in vitro was investigated. Treating the rats for three days with 0.05 μg/kg per day had no effect on basal PRL secretion, whereas the TRH-induced PRL secretion was increased (P < 0.001). The enhancing effect of 1,25(OH)2D3 was blunted by verapamil. Incubating dispersed anterior pituitary cells with 10−8 mol/l 1,25(OH)2D3 induced a significant increase in PRL secretion after 96 h (364 ± 30 ng/well vs 481 ± 33 ng/well, P < 0.001; mean ± sem) compared with control cells. The TRH-induced PRL secretion was increased in cells incubated with 1,25(OH)2D3 for 144 h (0.766 ± 0.061 vs 1.024 ± 0.076 μg/well, P < 0.05; mean ± sem) compared with control cells. Neither 25-hydroxyvitamin D3 (25OH-D3) nor 24,25-dihydroxyvitamin D3 had any effects on the PRL secretion. However, when the cells were incubated with both 10−8 mol/l 1,25(OH)2D3 and 10−6 mol/l 25OHD3, the enhancing effect of 1,25(OH)2D3 on the basal PRL secretion was blunted. The results suggest that 1,25(OH)2D3 possibly affects the regulation of PRL release from the rat pituitary and that this effect is specific for 1,25(OH)2D3.

scholarly journals Serum 25-hydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3 concentrations in adult dogs are more substantially increased by oral supplementation of 25-hydroxyvitamin D3 than by vitamin D3

2017 ◽  
Vol 6 ◽  
Author(s):  
Lauren R. Young ◽  
Robert C. Backus
Keyword(s):  
Vitamin D ◽  
Hplc Method ◽  
Vitamin D Status ◽  
Dihydroxyvitamin D3 ◽  
Oral Supplementation ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Supplementation Period ◽  
Single Cross ◽  
25 Hydroxyvitamin D

AbstractWe previously found a weak response in serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations when dogs were supplemented with oral vitamin D3 (D3). In the present study, we determined the relative potency of oral 25(OH)D3 compared with D3 for increasing vitamin D status in dogs with low serum 25(OH)D concentrations. Four male and three female, 4-year-old, intact, lean, genetically related, Chinese-crested/beagle dogs were studied in a randomised, single cross-over trial. After feeding a low-vitamin D diet (<4 IU/100 g) for 30 d, four dogs received daily D3 supplementation at 2·3 µg/kg body weight0·75, while three dogs received a molar equivalency as 25(OH)D3. The supplements, dissolved in ethanol, were applied to a commercial treat for consumption. Serum 25(OH)D3 and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) were analysed weekly using a validated HPLC method. Both supplementations increased (P ≤ 0·01) serum 25(OH)D3 concentrations. However, oral 25(OH)D3 resulted in greater (P < 0·0001) concentrations than D3 by week 1, with a difference of 173 % (P < 0·0001) by week 2. The supplementation period was limited to 14 d after serum 25(OH)D3 concentrations were not appearing to plateau. Thereafter, a washout period of 1 month separated the cross-over. Following 25(OH)D3, but not D3 supplementation, serum 24R,25(OH)2D3 concentrations increased (P ≤ 0·02), 3 to 5 weeks after initiating supplementation. Vitamin D status, as indicated by serum 25(OH)D3 and 24R,25(OH)2D3 concentrations, is more rapidly and efficiently increased in adult dogs by oral supplementation of 25(OH)D3 than D3.

Increased Circulatory Extrarenal 1α,25-Dihydroxyvitamin D3 in Bilaterally Nephrectomized Rats

2020 ◽  
Vol 20 (9) ◽  
pp. 1523-1530
Author(s):  
Murat Dabak ◽  
Durrin O. Dabak ◽  
Tuncay Kuloglu ◽  
Ersoy Baydar ◽  
Hakan Bulut ◽  
...  
Keyword(s):  
Immune Cells ◽  
Low Dose ◽  
Systemic Circulation ◽  
Bilateral Nephrectomy ◽  
Dihydroxyvitamin D3 ◽  
Hydroxyvitamin D ◽  
Inflammatory Conditions ◽  
Calcium Phosphorus ◽  
25 Hydroxyvitamin D

Background: Extrarenal 1α,25-dihydroxyvitamin D3 (1,25-D) locally produced by immune cells plays crucial roles in the regulation of the immune system. However, in vivo status of extrarenal 1,25-D and 25-hydroxyvitamin D (25-D) in acute inflammatory conditions are unknown. Objective: The aim of this study was to determine the extrarenal 1,25-D level in circulation in bilaterally nephrectomized rats, induced by low-dose lipopolysaccharide (LPS). Methods: Renal 1,25-D synthesis was terminated through bilateral nephrectomy in rats. The rats received intraperitoneal LPS (50 μg/kg BW) three times and the experiment was ended 24 hours after nephrectomy. Serum 1,25-D, 25-D, calcium, phosphorus, intact parathyroid hormone, and calcitonin levels were measured and immunohistochemistry was applied to detect the sources of extrarenal 1,25- D synthesis. Results: Circulatory 1,25-D concentration remarkably increased in both LPS-treated and non-treated bilaterally nephrectomized rats. Elevated circulatory 1,25-D did not have hypercalcemic endocrinal effects. The increased 1,25-D level also resulted in a concurrent rapid and dramatic depletion of circulatory 25-D. Conclusions: Extrarenal 1,25-D could enter into the systemic circulation and, therefore, might have systemic effects besides its autocrine and paracrine functions.

scholarly journals Vitamin D upregulates the macrophage complement receptor immunoglobulin in innate immunity to microbial pathogens

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Annabelle G. Small ◽  
Sarah Harvey ◽  
Jaspreet Kaur ◽  
Trishni Putty ◽  
Alex Quach ◽  
...  
Keyword(s):  
Vitamin D ◽  
Innate Immunity ◽  
Surface Expression ◽  
Microbial Pathogens ◽  
Cell Surface Expression ◽  
Complement Receptor ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Multistep Process ◽  
25 Hydroxyvitamin D

AbstractVitamin D deficiency remains a global concern. This ‘sunshine’ vitamin is converted through a multistep process to active 1,25-dihydroxyvitamin D3 (1,25D), the final step of which can occur in macrophages. Here we demonstrate a role for vitamin D in innate immunity. The expression of the complement receptor immunoglobulin (CRIg), which plays an important role in innate immunity, is upregulated by 1,25D in human macrophages. Monocytes cultured in 1,25D differentiated into macrophages displaying increased CRIg mRNA, protein and cell surface expression but not in classical complement receptors, CR3 and CR4. This was associated with increases in phagocytosis of complement opsonised Staphylococcus aureus and Candida albicans. Treating macrophages with 1,25D for 24 h also increases CRIg expression. While treating macrophages with 25-hydroxyvitamin D3 does not increase CRIg expression, added together with the toll like receptor 2 agonist, triacylated lipopeptide, Pam3CSK4, which promotes the conversion of 25-hydroxyvitamin D3 to 1,25D, leads to an increase in CRIg expression and increases in CYP27B1 mRNA. These findings suggest that macrophages harbour a vitamin D-primed innate defence mechanism, involving CRIg.

scholarly journals Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment

2016 ◽  
Vol 37 (5) ◽  
pp. 521-547 ◽  
Author(s):  
Peter J. Tebben ◽  
Ravinder J. Singh ◽  
Rajiv Kumar
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Active Form ◽  
Elevated Serum ◽  
Diagnosis And Treatment ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Stone Formers ◽  
25 Hydroxyvitamin D

AbstractHypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.

Serum 25-hydroxyvitamin D and vitamin D-binding protein levels and mineral metabolism after partial and total gastrectomy

1980 ◽  
Vol 79 (2) ◽  
pp. 255-258 ◽  
Author(s):  
Michio Imawari ◽  
Kunihisa Kozawa ◽  
Yasuo Akanuma ◽  
Sumihiko Koizumi ◽  
Hiroshige Itakura ◽  
...  
Keyword(s):  
Vitamin D ◽  
Total Gastrectomy ◽  
Mineral Metabolism ◽  
Binding Protein ◽  
Vitamin D Binding Protein ◽  
Hydroxyvitamin D ◽  
Protein Levels ◽  
25 Hydroxyvitamin D
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