1,25-Dihydroxyvitamin D regulates expression of the tryptophan hydroxylase 2 and leptin genes: implication for behavioral influences of vitamin D

We evaluated a novel assay for the measurement of 1,25 dihydroxyvitamin D (1,25 (OH)2D). Immunoextraction of 1,25 (OH)2D is performed using a mini column containing a solid-phase monoclonal antibody followed by radioimmunoassay (RIA) using an 125I-labelled 1,25 (OH)2D derivative tracer and Sac-cell separation. The mean recovery of 1,25(OH)2D3 was 101%, linearity was excellent, inter- and intra-assay coefficients of variation were 9, 8 and 13% and 11, 10 and 14% at low, medium and high concentrations of 1,25(OH)2D3, respectively. The cross-reactivity of vitamin D metabolites was <0·0015% for 25-hydroxyvitamin D3, 24, 25 dihydroxyvitamin D3 and dihydrotachysterol and 0·54% for lα calcidol. 1,25 dihydroxyvitamin D2 cross-reactivity was 79%. The detection limit of the assay was 5pmol/L. Comparison with a commercial radio receptor assay (RRA) and an in-house RIA gave regression equations of y = 0·94x+11·8 ( r = 0·98) and y = 0·91x-1·7 ( r = 0.95), respectively, with no major discrepancies between the methods in all patient groups studied. Plasma concentrations of 1,25 (OH)2D obtained with the assay were as follows: normal, unsupplemented subjects: mean 88, range 48–155 pmol/L, n = 68, patients with chronic renal failure: mean 11, range 3–36 pmol/L, n = 27, primary hyperparathyroidism: mean 198, range 130–299 pmol/L, n = 23, Paget's disease: mean 92, range 42–149 pmol/L, n = 24, osteomalacia: mean 43, range 27–61 pmol/L, n = 9. A minimum sample volume of 300 μL is required, the hands-on time is significantly less than other commercial assays and the measuring procedure is gamma counting rather than scintillation counting. The assay offers several advantages over previous methods and should allow more laboratories to offer measurement of 1,25 (OH)2D as part of their repertoire.

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Vitamin D Status among Thai School Children and the Association with 1,25-Dihydroxyvitamin D and Parathyroid Hormone Levels

PLoS ONE ◽

10.1371/journal.pone.0104825 ◽

2014 ◽

Vol 9 (8) ◽

pp. e104825 ◽

Cited By ~ 5

Author(s):

Lisa A. Houghton ◽

Andrew R. Gray ◽

Michelle J. Harper ◽

Pattanee Winichagoon ◽

Tippawan Pongcharoen ◽

...

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

School Children ◽

Vitamin D Status ◽

Hormone Levels ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D

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1,25-Dihydroxyvitamin D3 and Development of Tuberculosis in Cattle

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.10.6.1129-1135.2003 ◽

2003 ◽

Vol 10 (6) ◽

pp. 1129-1135 ◽

Cited By ~ 18

Author(s):

S. G. Rhodes ◽

L. A. Terry ◽

J. Hope ◽

R. G. Hewinson ◽

H. M. Vordermeier

Keyword(s):

Vitamin D ◽

T Cell ◽

Mononuclear Cells ◽

T Cell Proliferation ◽

Accessory Cell ◽

Dihydroxyvitamin D3 ◽

Dihydroxyvitamin D ◽

Cell Responses ◽

1,25 Dihydroxyvitamin D ◽

Accessory Cells

ABSTRACT This report describes the presence and activity of 1,25-dihydroxyvitamin D3 (1,25-D3) in experimental bovine tuberculosis. Animals that went on to develop tuberculous lesions exhibited a rapid transient increase in serum 1,25-D3 within the first 2 weeks following infection with Mycobacterium bovis. 1,25-D3-positive mononuclear cells were later identified in all tuberculous granulomas by immunohistochemical staining of postmortem lymph node tissue. These results suggest a role for 1,25-D3 both at the onset of infection and in the development of the granuloma in these infected animals. Using a monoclonal antibody to the vitamin D receptor (VDR) as a VDR agonist, we confirmed that activation of the vitamin D pathway profoundly depresses antigen-specific, but not mitogenic, bovine peripheral blood T-cell responses (proliferation and gamma interferon production). Investigation of the mechanism of this suppression showed that the VDR antibody modified the expression of CD80 by accessory cells, such that a significant positive correlation between T-cell proliferation and accessory cell CD80 emerged.

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Seasonal Variation in Serum 25-Hydroxy Vitamin D3 Does Not Affect 1,25-Dihydroxy Vitamin D

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456329403100105 ◽

1994 ◽

Vol 31 (1) ◽

pp. 31-34 ◽

Cited By ~ 31

Author(s):

T J Hine ◽

N B Roberts

Keyword(s):

Vitamin D ◽

Seasonal Variation ◽

Reference Range ◽

Seasonal Pattern ◽

Individual Variability ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

25 Hydroxy Vitamin D ◽

Time Periods ◽

Sunlight Hours

The seasonal variation of serum 25-hydroxy vitamin D3 and 1,25-dihydroxyvitamin D has been investigated. Blood was taken from 27 healthy volunteers, aged 21–44 years old at 3 monthly intervals over a period of 1 year. A scrolling monthly programme with 12 quarterly (3 month) time periods was developed. A summer associated increase in 25-hydroxy vitamin D3 was significantly correlated with but lagged behind by 2 months, the increase in recorded sunlight hours. However, four individuals showed no seasonal rise but maintained constant concentrations throughout the year within the established reference range. Serum 1,25-dihydroxy vitamin D showed marked intra-individual variability with no seasonal pattern although the highest concentration (180 pmol/L) was observed in the winter and no concentration greater than 108 pmol/L in the summer.

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Extrarenal synthesis of 1,25-dihydroxyvitamin D: Sensitivity to glucocorticoid treatment

Clinical Science ◽

10.1042/cs0720329 ◽

1987 ◽

Vol 72 (3) ◽

pp. 329-334 ◽

Cited By ~ 3

Author(s):

Silvano Adami ◽

G. Graziani ◽

D. Tartarotti ◽

R. Cappelli ◽

S. Casati ◽

...

Keyword(s):

Vitamin D ◽

Serum Calcium ◽

Glucocorticoid Treatment ◽

Prednisone Therapy ◽

Hydroxyvitamin D ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Prednisone Treatment ◽

Vitamin D Intoxication ◽

Before And After

1. The response of circulating 1,25-dihydroxyvitamin D [l,25-(OH)2D] to challenge with vitamin D treatment both before and after 7–10 days of prednisone therapy (25 mg/day) was investigated in five anephric subjects, six patients with chronic renal failure (CRF), two patients with vitamin D intoxication and four patients with hypoparathyroidism. 2. In anephric subjects serum 25-hydroxyvitamin D [25-(OH)D] rose from 58 ± 48 (sd) to 377±221 (sd) nmol/l after administration of 150 μg of 25-(OH)D3 for 1 month. Serum l,25-(OH)2D, which was barely detectable in only two out of five patients under basal conditions, rose to 30 ± 21 pmol/l after 2 weeks of therapy with 25-(OH)D3, but fell to 10 ± 5 pmol/l during prednisone treatment. 3. In CRF patients circulating l,25-(OH)2D rose from 37 ± 24 to 58 ± 24 pmol/l during 25-(OH)D3 therapy, but fell to 41 ± 31 pmol/l during prednisone treatment. In two patients with rheumatoid arthritis, hypercalcaemia due to vitamin D intoxication was associated with raised levels of 1,25-(OH)2D (288 and 317 pmol/l). Administration of prednisore resulted in suppression of l,25-(OH)2D levels (132 and 96 pmol/l respectively) and reduction of serum calcium to within the normal range. 4. In the hypoparathyroid patients prednisone therapy did not affect circulating 25-(OH)D levels but serum l,25-(OH)2D fell from 192 ± 42 to 117 ± 23 pmol/l and serum calcium from 2.41 ± 0.21 to 2.20 ± 0.05 mmol/l. 5. These findings indicate that a steroid sensitive extrarenal production of l,25-(OH)2D may occur in all subjects with a threshold serum concentration of the precursor 25-(OH)D.

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A Case of Vitamin-D-Dependent Rickets Type 1A with Normal 1,25-Dihydroxyvitamin D Caused by Two Novel Mutations of the CYP27B1 Gene

Hormone Research in Paediatrics ◽

10.1159/000446774 ◽

2016 ◽

Vol 87 (1) ◽

pp. 58-63 ◽

Cited By ~ 3

Author(s):

Aris Giannakopoulos ◽

Alexandra Efthymiadou ◽

Dionisios Chrysis

Keyword(s):

Vitamin D ◽

Novel Mutations ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D

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Mechanistic study of the cause of decreased blood 1,25-Dihydroxyvitamin D in sepsis

BMC Infectious Diseases ◽

10.1186/s12879-019-4529-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Chih-Huang Li ◽

Xiaolei Tang ◽

Samiksha Wasnik ◽

Xiaohua Wang ◽

Jintao Zhang ◽

...

Keyword(s):

Growth Hormone ◽

Vitamin D ◽

Growth Factor ◽

Kidney Failure ◽

Mechanistic Study ◽

Blood Levels ◽

Biological Functions ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Fgf 23

Abstract Background Vitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency. Methods We studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function. Results We demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver. Conclusions Because FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.

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