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.

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.

scholarly journals Dietary Phosphorus Transcriptionally Regulates 25-Hydroxyvitamin D-1α-Hydroxylase Gene Expression in the Proximal Renal Tubule

Endocrinology ◽  
2002 ◽  
Vol 143 (2) ◽  
pp. 587-595 ◽  
Author(s):  
Martin Y. H. Zhang ◽  
Xuemei Wang ◽  
Jonathan T. Wang ◽  
Nathalie A. Compagnone ◽  
Synthia H. Mellon ◽  
...  
Keyword(s):  
Renal Tubule ◽  
Hydroxylase Activity ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Proximal Renal Tubule ◽  
1,25 Dihydroxyvitamin D ◽  
Dietary Phosphorus ◽  
Straight Tubules ◽  
25 Hydroxyvitamin D ◽  
Bowman's Capsule

Abstract Synthesis of the hormone 1,25-dihydroxyvitamin D, the biologically active form of vitamin D, occurs in the kidney and is catalyzed by the mitochondrial cytochrome P450 enzyme, 25-hydroxyvitamin D-1α-hydroxylase (1α-hydroxylase). We sought to characterize the effects of changes in dietary phosphorus on the kinetics of renal mitochondrial 1α-hydroxylase activity and the renal expression of P450c1α and P450c24 mRNA, to localize the nephron segments involved in such regulation, and to determine whether transcriptional mechanisms are involved. In intact mice, restriction of dietary phosphorus induced rapid, sustained, approximately 6- to 8-fold increases in renal mitochondrial 1α-hydroxylase activity and renal P450c1α mRNA abundance. Immunohistochemical analysis of renal sections from mice fed the control diet revealed the expression of 1α-hydroxylase protein in the proximal convoluted and straight tubules, epithelial cells of Bowman’s capsule, thick ascending limb of Henle’s loop, distal tubule, and collecting duct. In mice fed a phosphorusrestricted diet, immunoreactivity was significantly increased in the proximal convoluted and proximal straight tubules and epithelial cells of Bowman’s capsule, but not in the distal nephron. Dietary phosphorus restriction induced a 2-fold increase in P450c1α gene transcription, as shown by nuclear run-on assays. Thus, the increase in renal synthesis of 1,25-dihydroxyvitamin D induced in normal mice by restricting dietary phosphorus can be attributed to an increase in the renal abundance of P450c1α mRNA and protein. The increase in P450c1α gene expression, which occurs exclusively in the proximal renal tubule, is due at least in part to increased transcription of the P450c1α gene.

Vitamin D and Calcitonin Treatment in Patients with Femoral Neck Fracture: A Prospective Controlled Clinical Study

1989 ◽  
Vol 17 (3) ◽  
pp. 226-242 ◽  
Author(s):  
E. Harju ◽  
R. Punnonen ◽  
R. Tuimala ◽  
J. Salmi ◽  
I. Paronen
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Serum Levels ◽  
Serum Calcitonin ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Age Related ◽  
Neck Fracture ◽  
25 Hydroxyvitamin D

The effects on general and bone metabolism of femoral neck fracture patients of 0.25 μg α-calcoid given orally twice daily ( n=9) and 25 μg calcitonin given subcutaneously 30 times ( n=10) in 10 weeks were studied against a control ( n=ll). Bone histology and histomorphometry showed non-age related osteoporosis in 30% and osteomalacia in 22% of the patients studied. Impaired serum vitamin D status was found in 47 – 88% of patients, secondary hyperparathyroidism and increased serum parathyroid hormone in 59% and decreased serum calcitonin levels in 69%. On histology, normal findings and non-age related osteoporosis on histology were associated with low serum levels of 25-hydroxyvitamin D3,1,25- and 24,25-dihydroxy vitamin D3. Very high serum levels of 1,25-dihydroxyvitamin D3 and low levels of 25-hydroxyvitamin D3 occurred in fracture patients with osteomalacia. Calcitonin improved calcium balance, reduced osteoporosis and increased the serum 1,25- and 24,25-dihydroxyvitamin D3 levels but had no effect on osteomalacia. Vitamin D reduced osteomalacia, slightly increased the serum 1,25-dihydroxyvitamin D3 concentration and decreased serum levels of parathyroid hormone. Both treatments gave a similar slight decrease in serum calcitonin concentrations. A mechanism of action for the treatments is suggested.

1α-Hydroxyvitamin D3 Treatment of Three Patients With 1,25-Dihydroxyvitamin D-Receptor-Defect Rickets and Alopecia

PEDIATRICS ◽  
1987 ◽  
Vol 80 (1) ◽  
pp. 97-101
Author(s):  
E. Takeda ◽  
Y. Kuroda ◽  
T. Saijo ◽  
E. Naito ◽  
H. Kobashi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Calcium Lactate ◽  
Type Ii ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

Three patients with clinically different severities of vitamin D-dependent rickets, type II, with alopecia, which is 1,25-dihydroxyvitamin D-receptor-defect rickets and is particularly resistant to treatment with calciferol analogues, were treated with large doses of lα-hydroxyvitamin D3 (1α-(OH)D3) and 2 g of calcium lactate. Except for the alopecia, all of the abnormalities of patients 1 and 2 were reversed by treatment with 3 µg/kg/d of 1α-(OH)D3, and those of patient 3, who had the severest manifestations, were reversed by treatment with 6 µg/kg/d. The serum 24,25-dihydroxyvitamin D concentrations of the three patients were low before treatment and those of patients 1 and 2 increased during treatment. These findings suggest that in patients 1 and 2, 25-hydroxyvitamin D-24-hydroxylase was stimulated via a 1,25-dihydroxyvitamin D-receptor-mediated system by treatment with 1α-(OH)D3.

Simultaneous determination of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D in plasma or serum.

1981 ◽  
Vol 27 (10) ◽  
pp. 1757-1760 ◽  
Author(s):  
M J Jongen ◽  
W J van der Vijgh ◽  
H J Willems ◽  
J C Netelenbos ◽  
P Lips
Keyword(s):  
Vitamin D ◽  
Vitamin D Metabolites ◽  
Binding Assays ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Extraction And Purification ◽  
Chromatographic Procedure ◽  
25 Hydroxyvitamin D ◽  
Liquid Chromatographic

Abstract We describe a simultaneous assay for the principal vitamin D metabolites: 25-hydroxyvitamin D, 24-25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D. Special attention has been paid to simplification of the extensive extraction and purification procedures used in previously described simultaneous assays. All three metabolites were isolated with a single extraction step, followed by only one gradient liquid-chromatographic procedure. For final quantitation we used competitive protein binding assays, involving readily available binding proteins and commercially purchased tritiated vitamin D metabolites. Concentrations in the plasma of healthy subjects (mean age, 27 years), sampled during December were 51 (SD 17) nmol/L, 4.1 (SD 1.3) nmol/L, and 124 (SD 26) pmol/L for 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D, respectively. Intra- and interassay CVs for the three metabolites were 4.4 and 3.9%, 6.7 and 8.0%, and 7.0 and 4.8%, respectively.

Determinants of the serum concentration of 1,25-dihydroxyvitamin D in primary hyperparathyroidism

1989 ◽  
Vol 76 (1) ◽  
pp. 81-86 ◽  
Author(s):  
B. C. Lalor ◽  
E. B. Mawer ◽  
M. Davies ◽  
G. A. Lumb ◽  
L. Hunt ◽  
...  
Keyword(s):  
Vitamin D ◽  
Serum Concentration ◽  
Primary Hyperparathyroidism ◽  
Serum Concentrations ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Relevant Variables ◽  
Biological Determinants ◽  
25 Hydroxyvitamin D

1. The serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 44 patients with primary hyperparathyroidism. 2. In 14 patients the serum concentration of 1,25-dihydroxyvitamin D was greater than normal (142–337 pmol/l). One patient had a subnormal concentration of 1,25-dihydroxyvitamin D (36 pmol/l) but no other evidence of vitamin D deficiency. 3. The possible biological determinants of the serum concentration of 1,25-dihydroxyvitamin D were sought by multivariate analysis of relevant variables. The serum concentration of 1,25-dihydroxyvitamin D was found to be significantly and positively correlated with the serum concentrations of 25-hydroxyvitamin D (P < 0.001) and parathyroid hormone (P < 0.003), and with the glomerular filtration rate (P < 0.03), and negatively correlated with the serum concentrations of calcium (P < 0.02) and phosphate (P = 0.055) (multiple R = 0.638,P < 0.002). 4. In primary hyperparathyroidism the major determinant of serum 1,25-dihydroxyvitamin D is the availability of precursor 25-hydroxyvitamin D. 5. The finding that serum 1,25-dihydroxyvitamin D is commonly normal in patients with primary hyperparathyroidism despite an adequate state of vitamin D nutrition, can be explained in terms of the constraining influences of hypercalcaemia and variable degrees of renal dysfunction on the biosynthesis of 1,25-dihydroxyvitamin D.

scholarly journals Vitamin D Regulation, Metabolism, AndFunction

2020 ◽  
Author(s):  
MARINA GERGES
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Uv Light ◽  
The Body ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
A Cell ◽  
25 Hydroxyvitamin D ◽  
Made In

Interest in vitamin D has dramatically increased over the past several decades. From the beginning, vitamin D was incorrectly named a vitamin when later it was discovered to be a member of the steroid hormone family. Over time, the vitamin D receptor was discovered along with its major circulating form, 25-hydroxyvitamin D, and its the hormonal ligand, 1,25-dihydroxyvitamin D. Classically, vitamin D was known to be important for enhancing intestinal absorption of calcium; however, interest grew in vitamin D when it was determined that vitamin D may be utilized by other tissues of the body. Vitamin D3 is made in the skin from 7-dehydrocholesterol under the influence of UV light. Vitamin D2 (ergocalciferol) is derived from the plant sterol ergosterol. Vitamin D is metabolized first to 25 hydroxyvitamin D (25OHD), then to the hormonal form 1,25- dihydroxyvitamin D (1,25(OH)2D). CYP2R1 is the most important 25-hydroxylase; CYP27B1 is the key 1-hydroxylase. Both 25OHD and 1,25(OH)2D are catabolized by CYP24A1. 1,25(OH)2D is the ligand for the vitamin D receptor (VDR), a transcription factor, binding to sites in the DNA called vitamin D response elements (VDREs). There are thousands of these binding sites regulating hundreds of genes in a cell-specific fashion. VDR-regulated transcription is dependent on modulators, the profile of which is also cell-specific. Analogs of 1,25(OH)2D are being developed to target specific diseases with minimal side effects.(Bikle , 2014)

scholarly journals Influence of physical mobility and season on 25-hydroxyvitamin D-parathyroid hormone interaction and bone remodelling in the elderly

2000 ◽  
pp. 673-679 ◽  
Author(s):  
R Theiler ◽  
HB Stahelin ◽  
M Kranzlin ◽  
G Somorjai ◽  
L Singer-Lindpaintner ◽  
...  
Keyword(s):  
Vitamin D ◽  
The Elderly ◽  
Serum Concentrations ◽  
Institutionalized Elderly ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Physical Mobility ◽  
25 Hydroxyvitamin D ◽  
Mobility Status

OBJECTIVE: To investigate influences of physical mobility and season on 25-hydroxyvitamin D-intact parathyroid hormone (iPTH) interaction in the elderly. DESIGN: We examined 188 frail institutionalized elderly at the expected nadir of their serum vitamin D concentrations (winter). This group was compared with 309 healthy ambulatory elderly at the expected time of maximum vitamin D repletion (summer), to accentuate the influences of season and physical activity. METHODS: Serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, iPTH and urinary deoxypyridinoline (DPD) were measured. RESULTS: Vitamin D metabolites were significantly lower in the institutionalized elderly (P<0.0001), with an 82.5% prevalence of vitamin D deficiency (25-hydroxyvitamin D <12ng/ml) in institutionalized elderly in wintertime and 15.5% in ambulatory elderly in summertime. Overall, median iPTH did not differ between groups. However, median iPTH secretion in the presence of low vitamin D serum concentrations (5-30ng/ml) was greater in ambulatory elderly. This could be explained by lower mobility status being correlated with greater serum calcium concentrations (r=0.24, P=0.02 in women; r=0.35, P=0. 001 in men) and greater urinary excretion of DPD (r=0.41, P=0.0001 in women; r=0.42, P=0.0002 in men), independent of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and iPTH. CONCLUSIONS: These data support the hypothesis that immobility, even in the presence of vitamin D deficiency, acts as an overriding influence on bone metabolism by promoting bone resorption (measured as urinary DPD) and increasing serum calcium independent of iPTH. Therefore mobility status may substantially affect 25-hydroxyvitamin D threshold values and the degree to which patients benefit from vitamin supplementation.

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