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.

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 IGF-I and GH stimulate Phex mRNA expression in lungs and bones and 1,25-dihydroxyvitamin D(3) production in hypophysectomized rats

2002 ◽  
pp. 97-105 ◽  
Author(s):  
E Zoidis ◽  
M Gosteli-Peter ◽  
C Ghirlanda-Keller ◽  
L Meinel ◽  
J Zapf ◽  
...  
Keyword(s):  
Vitamin D ◽  
Mrna Expression ◽  
Type I ◽  
Serum Osteocalcin ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Igf I ◽  
Hypophysectomized Rats ◽  
25 Hydroxyvitamin D

OBJECTIVE: X-linked hypophosphatemia, a renal phosphate (Pi)-wasting disorder with defective bone mineralization, is caused by mutations in the PHEX gene (a Pi-regulating gene with homology to endopeptidases on the X chromosome). We wondered whether changes in Phex and neprilysin (NEP) (another member of the family of zinc endopeptidases) mRNA expression could be observed in relation to vitamin D and Pi metabolism during GH- and IGF-I-stimulated growth of hypophysectomized rats. DESIGN: Animals were infused s.c. for 2 days with vehicle, 200 mU (67 microg) GH or 300 microg IGF-I/rat per 24 h. We determined serum osteocalcin and osteocalcin mRNA in bone, Phex mRNA in bone and lungs, serum 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) and serum Pi levels, and renal expression of 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-hydroxylase), of 25-hydroxyvitamin D(3)-24-hydroxylase (24-hydroxylase) and of the Na-dependent Pi-cotransporter type I and II (Na(d)Pi-I and -II). RESULTS: As compared with vehicle-treated controls, body weight and tibial epiphyseal width significantly increased in GH- and IGF-I-treated animals. Serum osteocalcin and osteocalcin mRNA levels in bone, Phex mRNA in bone and lungs, serum 1,25-(OH)(2)D(3) and renal 1alpha-hydroxylase mRNA rose concomitantly, whereas expression of NEP in lungs was barely affected and renal 24-hydroxylase mRNA decreased. Na(d)Pi-I and -II gene expression in the kidney and serum Pi levels remained unchanged. CONCLUSIONS: Our findings suggest a coordinate regulation of Phex mRNA expression in lungs and bone and vitamin D metabolism during GH- and IGF-I-stimulated growth.

scholarly journals Age-related alteration of vitamin D metabolism in response to low-phosphate diet in rats

2005 ◽  
Vol 93 (3) ◽  
pp. 299-307 ◽  
Author(s):  
Tsui-Shan Chau ◽  
Wan-Ping Lai ◽  
Pik-Yuen Cheung ◽  
Murray J. Favus ◽  
Man-Sau Wong
Keyword(s):  
Vitamin D ◽  
Mrna Expression ◽  
Age Groups ◽  
Metabolic Clearance ◽  
Adult Rats ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Age Related ◽  
25 Hydroxyvitamin D

The responses of renal vitamin D metabolism to its major stimuli alter with age. Previous studies showed that the increase in circulating 1,25-dihydroxyvitamin D (1,25(OH)2D3) as well as renal 25-hydroxyvitamin D3 1-α hydroxylase (1-OHase) activity in response to dietary Ca or P restriction reduced with age in rats. We hypothesized that the mechanism involved in increasing circulating 1,25(OH)2D3 in response to mineral deficiency alters with age. In the present study, we tested the hypothesis by studying the expression of genes involved in renal vitamin D metabolism (renal 1-OHase, 25-hydroxyvitamin D 24-hydroxylase (24-OHase) and vitamin D receptor (VDR)) in young (1-month-old) and adult (6-month-old) rats in response to low-phosphate diet (LPD). As expected, serum 1,25(OH)2D3 increased in both young and adult rats upon LPD treatment and the increase was much higher in younger rats. In young rats, LPD treatment decreased renal 24-OHase (days 1–7, P<0·01) and increased renal 1-OHase mRNA expression (days 1–5, P<0·01). LPD treatment failed to increase renal 1-OHase but did suppress 24-OHase mRNA expression (P<0·01) within 7 d of LPD treatment in adult rats. Renal expression of VDR mRNA decreased with age (P<0·001) and was suppressed by LPD treatment in both age groups (P<0·05) Feeding of adult rats with 10 d of LPD increased 1-OHase (P<0·05) and suppressed 24-OHase (P<0·001) as well as VDR (P<0·05) mRNA expression. These results indicate that the increase in serum 1,25(OH)2D3 level in adult rats during short-term LPD treatment is likely to be mediated by a decrease in metabolic clearance via the down-regulation of both renal 24-OHase and VDR expression. The induction of renal 1-OHase mRNA expression in adult rats requires longer duration of LPD treatment than in younger rats.

Vitamin D Metabolism in Osteogenesis Imperfecta During Calcitonin Therapy

PEDIATRICS ◽  
1984 ◽  
Vol 73 (4) ◽  
pp. 538-542
Author(s):  
Yoshikazu Nishi ◽  
Sumio Hyodo ◽  
Kazunori Yoshimitsu ◽  
Kunihiko Sawano ◽  
Kanji Yamaoka ◽  
...  
Keyword(s):  
Vitamin D ◽  
Osteogenesis Imperfecta ◽  
Plasma Concentrations ◽  
Mean Value ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
The Mean ◽  
Acute And Chronic Effects

The effect of calcitonin on plasma concentrations of 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] was studied in six patients with osteogenesis imperfecta. The mean pretreatment value of plasma 1,25-(OH)2D was significantly higher than the mean value of age-matched control subjects (P &lt; .05). High or normal plasma levels of 1,25-(OH)2D before calcitonin therapy were decreased after 1 month of therapy and remained normal thereafter in all six patients. Plasma 25-hydroxyvitamin D concentrations, which were normal before calcitonin injection, remained normal during calcitonin administration. These results indicate that there may be acute and chronic effects of calcitonin on vitamin D metabolism.

Plasma concentrations of vitamin D metabolites in pubertal girls with anorexia nervosa

1986 ◽  
Vol 113 (4_Suppl) ◽  
pp. S458-S467 ◽  
Author(s):  
D. AARSKOG ◽  
L. AKSNES ◽  
T. MARKESTAD ◽  
O. TRYGSTAD
Keyword(s):  
Vitamin D ◽  
Anorexia Nervosa ◽  
Binding Protein ◽  
Plasma Concentrations ◽  
Similar Data ◽  
Vitamin D Binding Protein ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

ABSTRACT Plasma concentrations of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2D), 24,25-dihydroxyvitamin D (24,25-(OH)2D) and vitamin D-binding protein (DBP) were measured in 12 pubertal girls (aged 10-18 yr) with anorexia nervosa in relapse. The results were compared with similar data obtained in 81 healthy girls representing all stages of puberty. The patients with anorexia nervosa had significantly lower 1,25-(OH)2D levels (71 vs. 124 pmol/l; p<0.0005), and significantly higher 24,25-(OH)2D levels (6.0 vs. 3.2 nmol/l; p<0.0005), whereas the 25-OHD concentrations were similar in the two groups (85.7 vs. 86.7 nmol/l). The molar ratios of 24,25-(OH)2D to 25-OHD, which reflects the relative activity of the 24-hydroxylation, were significantly higher in the anorectics (6.6 % vs. 3.6 %; p<0.0005). The mean level of DBP did not differ between the two groups, and accordingly the calculated "free-fraction of 1,25-(OH)2 D" was significantly lower in the anorectic patients (p<0.0005). It appears that the regulatory mechanisms of the vitamin D endocrine system are altered in the patients with anorexia nervosa at puberty resulting in a relative decrease of the plasma concentration of 1,25-(OH)2D and increase of the 24,25-(OH)2D concentration. Key words: Anorexia nervosa, vitamin D metabolism, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, vitamin D binding protein

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.

Responses of serum calcium and phosphorus in the frog Rana tigrina to injection of various vitamin D analogs

1987 ◽  
Vol 65 (8) ◽  
pp. 2111-2112 ◽  
Author(s):  
Ajai K. Srivastav ◽  
L. Rani ◽  
K. Swarup
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Vitamin D Analogs ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Rana Tigrina ◽  
Calcium Deposits ◽  
25 Hydroxyvitamin D ◽  
Calcium And Phosphorus

Intraperitoneal injections of either vitamin D3 (4 IU/100 g body wt.), 25 hydroxyvitamin D3 (100 ng/100 g body wt.), or 1,25 dihydroxyvitamin D3 (100 ng/100 g body wt.) for 15 days induced hypercalcemia, hyperphosphatemia, and depletion of calcium deposits in the paravertebral lime sacs in an anuran, Rana tigrina.

Cyclosporin a and Vitamin D Metabolism: Studies in Patients with Psoriasis and in Rats

1994 ◽  
Vol 86 (5) ◽  
pp. 627-632 ◽  
Author(s):  
A. J. Shaw ◽  
M. E. Hayes ◽  
M. Davies ◽  
B. D. Edwards ◽  
F. W. Ballardie ◽  
...  
Keyword(s):  
Vitamin D ◽  
Synovial Fluid ◽  
Cyclosporin A ◽  
Severity Index ◽  
Hydroxylase Activity ◽  
Local Synthesis ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

1. Cyclosporin A, an immunosuppressive drug used to treat psoriasis, stimulates renal synthesis of 1,25-dihydroxyvitamin D in rats. 1,25-Dihydroxy vitamin D can also reduce the activity of psoriasis, and in the present study we have examined the possibility that cyclosporin A mediates some of its actions in psoriasis by renal or extra-renal production of 1,25-dihydroxyvitamin D. 2. Treatment of 12 psoriatic patients with cyclosporin A (5 mg day−1 kg−1) for 3 months significantly improved the psoriasis activity and severity index and reduced glomerular filtration rate, but serum 1,25-dihydroxyvitamin D levels were not changed. However, 1–3 months after stopping cyclosporin A treatment, an increase in the psoriasis activity and severity index score was accompanied by a small, but significant, increase in serum 1,25-dihydroxyvitamin D concentration. Plasma 1,25-dihydroxyvitamin D levels in rats gavaged with cyclosporin A (15 mg day−1 kg−1 for 2 weeks) were significantly increased compared with controls, but a lower dose of cyclosporin A (2.4 mg day−1 kg−1) had no effect. Renal 25-hydroxyvitamin D-24-hydroxylase activity in rat kidney homogenates was not different between control and cyclosporin A-treated rats. Renal 25-hydroxyvitamin D-1α-hydroxylase activity was not detectable in these homogenates. Extra-renal production of 1,25-dihydroxyvitamin D by activated macrophages isolated from the synovial fluid of patients with inflammatory arthritis was reduced after incubation with cyclosporin A (0.1–10 μmol/l) for 30 h or 5 days. 3. It is unlikely that alteration of circulating 1,25-dihydroxyvitamin D concentration is one of the modes of action of cyclosporin A in psoriasis. Since cyclosporin A inhibits 1,25-dihydroxyvitamin D production by activated synovial fluid macrophages, it is unlikely that cyclosporin A mediates some of its therapeutic actions by local synthesis of 1,25-dihydroxyvitamin D within the psoriatic lesion.

Side-chain oxidation of vitamin D3 in mouse kidney mitochondria: effect of the Hyp mutation and 1,25-dihydroxyvitamin D3 treatment

1987 ◽  
Vol 65 (10) ◽  
pp. 853-859 ◽  
Author(s):  
Glenville Jones ◽  
Agatha Yip ◽  
Harriet S. Tenenhouse
Keyword(s):  
Enzyme Activity ◽  
Mouse Kidney ◽  
Side Chain ◽  
Mitochondrial Enzyme ◽  
Renal Metabolism ◽  
Chain Oxidation ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

Side-chain oxidation of vitamin D is an important degradative pathway. In the present study we compared the enzymes involved in side-chain oxidation in normal and Hyp mouse kidney. Homogenates of normal mouse kidney catalyze the conversion of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3, 24-oxo-25-hydroxyvitamin D3, and 24-oxo-23,25-dihydroxyvitamin D3. After subcellular fractionation, total side-chain oxidative activity, estimated by the sum of the three products synthesized per milligram protein under initial rate conditions, coincided with the mitochondrial enzyme marker succinate–cytochrome-c reductase. Treatment of normal mice with 1,25-dihydroxyvitamin D3 (1.5 ng/g) resulted in an eightfold increase in mitochondrial enzyme activity, with no change in apparent Km but a significant rise in Vmax. With 24,25-dihydroxyvitamin D3 as the substrate, normal renal mitochondria produced 24-oxo-25-hydroxyvitamin D3 and 24-oxo-23,25-dihydroxyvitamin D3, and the synthesis of these metabolites could be increased sixfold by pretreatment with 1,25-dihydroxyvitamin D3. In the Hyp mouse, the side-chain oxidation pathway showed similar subcellular distribution of enzyme activity. However, product formation from 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 was twofold greater in mutant than in normal mitochondria. Furthermore, 1,25-dihydroxyvitamin D3 pretreatment of Hyp mice resulted in a 3.4-fold increase over basal metabolism of both 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3. These results demonstrate that (i) kidneys from normal and Hyp mice possess basal and 1,25-dihydroxyvitamin D3 inducible enzyme system(s) in the mitochondrial fraction, which catalyze the side-chain oxidation of 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3, and (ii) the Hyp mutation appears to perturb the renal metabolism of both substrates only in the basal state.

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