scholarly journals Abnormal parathyroid hormone stimulation of 25-hydroxyvitamin D-1 alpha-hydroxylase activity in the hypophosphatemic mouse. Evidence for a generalized defect of vitamin D metabolism.

1986 ◽  
Vol 77 (1) ◽  
pp. 181-187 ◽  
Author(s):  
T Nesbitt ◽  
M K Drezner ◽  
B Lobaugh
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Hydroxylase Activity ◽  
Vitamin D Metabolism ◽  
Hormone Stimulation ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Stimulation Of

scholarly journals Conflicting actions of parathyroid hormone-related protein and serum calcium as regulators of 25-hydroxyvitamin D(3)-1 alpha-hydroxylase expression in a nude rat model of humoral hypercalcemia of malignancy

2001 ◽  
Vol 171 (2) ◽  
pp. 249-257 ◽  
Author(s):  
T Michigami ◽  
H Yamato ◽  
H Suzuki ◽  
Y Nagai-Itagaki ◽  
K Sato ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Related Protein ◽  
Humoral Hypercalcemia Of Malignancy ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Humoral Hypercalcemia ◽  
Parathyroid Hormone Related Protein ◽  
Severe Hypercalcemia ◽  
25 Hydroxyvitamin D

In patients with humoral hypercalcemia of malignancy (HHM), serum levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) are generally low, although the pathophysiology of the impaired vitamin D metabolism is not fully understood. In the present study, we have investigated vitamin D metabolism in our newly developed rat model of HHM in which a human infantile fibrosarcoma producing parathyroid hormone-related protein (PTHrP), named OMC-1, was inoculated s.c. into athymic nude rats. In OMC-1-bearing rats, the serum concentration of 1,25(OH)(2)D was markedly reduced when the animals exhibited severe hypercalcemia (Ca > or =15 mg/dl), while it was rather elevated in those with mild hypercalcemia. To further examine whether serum Ca levels affect 1,25(OH)(2)D concentration, we administered bisphosphonate YM529 to OMC-1-bearing rats when they exhibited severe hypercalcemia. The restoration of the serum Ca level by administration of YM529 was accompanied by a marked increase in the 1,25(OH)(2)D level, suggesting that the serum Ca level itself plays an important role in the regulation of the 1,25(OH)(2)D level in these rats. On the other hand, when the OMC-1-bearing rats were treated with a neutralizing antibody against PTHrP, serum 1,25(OH)(2)D levels remained low despite the reduction in serum Ca levels. Expression of 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) in kidney was decreased in OMC-1-bearing rats with severe hypercalcemia, and markedly enhanced after treatment with bisphosphonate. This enhancement in 1 alpha-hydroxylase expression was not observed after treatment with the antibody against PTHrP. These results suggest that PTHrP was responsible for the enhanced expression of 1 alpha-hydroxylase in YM529-treated rats, and that hypercalcemia played a role in reducing the serum 1,25(OH)(2)D level in OMC-1-bearing rats by suppressing the PTHrP-induced expression of the 1 alpha-hydroxylase gene.

Dissociation of phosphaturia and 25(OH)D-1 alpha-hydroxylase trophism using a novel analogue of parathyroid hormone

1992 ◽  
Vol 262 (4) ◽  
pp. E483-E487 ◽  
Author(s):  
T. O. Carpenter ◽  
M. D. McPhee ◽  
R. Bort ◽  
M. A. Mitnick ◽  
D. L. Carnes
Keyword(s):  
Parathyroid Hormone ◽  
High Performance ◽  
Phosphate Transport ◽  
Hydroxylase Activity ◽  
Renal Handling ◽  
Hydroxyvitamin D ◽  
C57bl Mice ◽  
25 Hydroxyvitamin D ◽  
Stimulation Of

Certain parathyroid hormone (PTH) analogues have been shown to selectively impair some but not all physiological actions of PTH. In this study, transaminated rat (r) PTH [TA-rPTH-(1-34)], a PTH analogue that differs from the rPTH-(1-34) fragment in that the NH2-terminal alanine is converted to pyruvate, was infused into mice to determine its properties in vivo and specifically to determine whether stimulation of 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) activity was more dependent on concomitant renal handling of phosphate or on generation of adenosine 3',5'-cyclic monophosphate (cAMP). High-performance liquid chromatography-purified TA-rPTH-(1-34) was infused into C57BL mice at 10 or 30 pmol/h for 24 h. At 30 pmol/h, TA-rPTH-(1-34) was comparable with rPTH-(1-34) in its hypophosphatemic and phosphaturic effects but was less potent than rPTH-(1-34) in raising serum calcium. TA-rPTH-(1-34) was markedly less effective in stimulating renal 1 alpha-hydroxylase than rPTH-(1-34). Stimulation of urinary cAMP excretion occurred after infusion with TA-rPTH-(1-34), but this effect was significantly less than that seen with rPTH-(1-34). These findings indicate that PTH-induced hypophosphatemia and phosphaturia can be uncoupled from PTH stimulation of 1 alpha-hydroxylase. Furthermore, cAMP-related signal transduction appears to be more significant in regulation of 1 alpha-hydroxylase than mechanisms that mediate PTH-sensitive phosphate transport, independent of cAMP.

scholarly journals Race, Ancestry, and Vitamin D Metabolism: The Multi-Ethnic Study of Atherosclerosis

2020 ◽  
Vol 105 (12) ◽  
pp. e4337-e4350
Author(s):  
Simon Hsu ◽  
Andrew N Hoofnagle ◽  
Deepak K Gupta ◽  
Orlando M Gutierrez ◽  
Carmen A Peralta ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
European Ancestry ◽  
Vitamin D Metabolism ◽  
Ethnic Study ◽  
Hydroxyvitamin D ◽  
Mineral Homeostasis ◽  
25 Hydroxyvitamin D ◽  
Race Ethnicity ◽  
Racial Ethnic

Abstract Context A comprehensive characterization of racial/ethnic variations in vitamin D metabolism markers may improve our understanding of differences in bone and mineral homeostasis and the risk of vitamin D–related diseases. Objective Describe racial/ethnic differences in vitamin D metabolism markers and their associations with genetic ancestry. Design, Setting, Participants In a cross-sectional study within the Multi-Ethnic Study of Atherosclerosis (MESA), we compared a comprehensive panel of vitamin D metabolism markers across self-reported racial/ethnic groups of Black (N = 1759), White (N = 2507), Chinese (N = 788), and Hispanic (N = 1411). We evaluated associations of proportion African and European ancestry with this panel of markers in Black and Hispanic participants using ancestry informative markers. Latent class analysis evaluated associations between patterns of vitamin D measurements with race/ethnicity. Results Compared with Black participants, White participants had significantly higher serum concentrations of 25-hydroxyvitamin D and fibroblast growth factor-23; lower concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D; circulating vitamin D metabolite ratios suggesting lower CYP27B1 and higher CYP24A1 activity; higher urinary concentrations of calcium and phosphorus with higher urinary fractional excretion of phosphorus; and differences in vitamin D binding globulin haplotypes. Higher percent European ancestry was associated with higher 25-hydroxyvitamin D and lower parathyroid hormone concentrations among Black and Hispanic participants. Latent classes defined by vitamin D measurements reflected these patterns and differed significantly by race/ethnicity and ancestry. Conclusions Markers of vitamin D metabolism vary significantly by race/ethnicity, may serve to maintain bone and mineral homeostasis across ranges of 25-hydroxyvitamin D production, and be attributable, at least partly, to genetic ancestry.

Effect of magnesium depletion on metabolism of 25-hydroxyvitamin D in rats

1987 ◽  
Vol 253 (1) ◽  
pp. E106-E113
Author(s):  
T. O. Carpenter ◽  
D. L. Carnes ◽  
C. S. Anast
Keyword(s):  
Vitamin D ◽  
Animal Studies ◽  
Magnesium Deficiency ◽  
Hydroxylase Activity ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Magnesium Depletion ◽  
25 Hydroxyvitamin D

Resistance to vitamin D in magnesium depletion has been observed in humans and in animal studies. Variable levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] have been reported in patients with magnesium depletion, and studies of vitamin D metabolism in states of magnesium depletion have not yielded consistent results. We examined effects of magnesium deprivation on circulating 1,25(OH)2D levels before and after a loading dose of 25-hydroxyvitamin D3 [25(OH)D3], on in vivo conversion of small doses of radiolabeled 25(OH)D3 to 1,25(OH)2D3 in intact rats, and on in vitro 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) activity in rat renal mitochondria. The effects of magnesium-free media on mitochondrial 1 alpha-hydroxylase activity was examined. Magnesium depletion did not affect in vivo conversion of 25(OH)D to 1,25(OH)2D. In vitro 1 alpha-hydroxylase activity was comparable in magnesium-replete and -deplete animals and was evident in the absence of added magnesium in incubation media. Our in vivo and in vitro studies are consistent with one another and demonstrate that in the rat conversion of 25(OH)D to 1,25(OH)2D is unimpaired in magnesium deficiency. Resistance to vitamin D in magnesium depletion is likely due to the impaired skeletal responsivity to 1,25(OH)2D, as demonstrated in earlier studies.

scholarly journals Plasma 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and parathyroid hormone in familial hypocalciuric hypercalcemia and primary hyperparathyroidism

2008 ◽  
Vol 159 (6) ◽  
pp. 719-727 ◽  
Author(s):  
Signe Engkjær Christensen ◽  
Peter H Nissen ◽  
Peter Vestergaard ◽  
Lene Heickendorff ◽  
Lars Rejnmark ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Plasma Levels ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

IntroductionFamilial hypocalciuric hypercalcemia (FHH) is a lifelong, benign, inherited condition caused by inactivating mutations in the calcium-sensing receptor (CASR) gene. Both FHH and primary hyperparathyroidism (PHPT) are characterized by elevated P-calcium, normal or elevated plasma-parathyroid hormone (P-PTH), and typically normal renal function. In PHPT, vitamin D metabolism is typically characterized by low plasma levels of 25-hydroxyvitamin D (25OHD), and high plasma levels of 1,25-dihydroxyvitamin D (1,25(OH)2D). In FHH, the vitamin D metabolism is not very well known.ObjectiveTo compare and evaluate plasma 25OHD, 1,25(OH)2D, and PTH in FHH and PHPT.DesignCross-sectional study.MaterialsAbout 66 FHH patients with mutations in the CASR gene, 147 patients with surgically verified PHPT, and 46 controls matched to FHH patients according to age (±5 years), sex, and season. All patients had a P-creatinine <140 μmol/l.MethodsWe measured P-calcium, P-Ca2+, P-albumin, P-creatinine, P-phosphate, P-magnesium, and P-PTH by standard laboratory methods. P-25OHD and P-1,25(OH)2D were measured by RIA or enzyme immunoassay. In FHH, all protein-coding exons in the CASR gene were sequenced and aligned to GenBank reference sequence .ResultsPHPT patients had higher body mass index (2p<0.01), together with higher P-PTH (2p<0.01) and P-1,25(OH)2D (2p<0.01) compared with FHH patients. The groups had similar levels of P-Ca2+ and of P-25OHD. The phenotypic expression of the CASR mutations (as determined by the degree of hypercalcemia) did not influence the levels of P-1,25(OH)2D.ConclusionEven though P-calcium and P-25OHD were comparable, P-1,25(OH)2D and P-PTH differed between FHH and PHPT.

Vitamin D Dose Response Study: Effect on Serum 25-Hydroxyvitamin D and Parathyroid Hormone

2011 ◽  
pp. S60-1-S60-1
Author(s):  
J Christopher Gallagher ◽  
Adarsh Sai ◽  
Thomas J Templin ◽  
Lynette M Smith
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Dose Response ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Dose Response Study

scholarly journals P431 Vitamin D binding protein in the limelight: IBD-related inflammation and circulating levels of vitamin D binding protein, total, free and bioavailable 25-hydroxyvitamin D

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S393-S393
Author(s):  
A Aksan ◽  
K Böttger ◽  
N Hein ◽  
Y Caicedo-Zea ◽  
I Diehl ◽  
...  
Keyword(s):  
Vitamin D ◽  
Binding Protein ◽  
Transferrin Saturation ◽  
Simultaneous Detection ◽  
Full Blood Count ◽  
Vitamin D Binding Protein ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Vitamin D Levels ◽  
25 Hydroxyvitamin D

Abstract Background Vitamin D deficiency occurs frequently in patients with Crohn’s disease (CD) and ulcerative colitis (UC). While recent cohort studies support an association of vitamin D with important clinical parameters and outcomes in IBD, the complex interplay of inflammation with vitamin D metabolism in IBD poses a viscious circle. We sought to further illucidate the relation between inflammation and different vitamin D parameters. To the best our knowledge, this was the first study to focus on the relationship between vitamin D binding protein (VDBP), circulating total, free, and bioavailable 25-hydroxyvitamin D (25(OH)D), and inflammation, in adult IBD patients. Methods This was a comparative, single-centred, cross-sectional study in patients with IBD aged 18–65 years. Full blood count, transferrin, albumin and hsCRP were determined by standard methods. The presence/absence of inflammation was assessed based on serum hsCRP levels (cutoff &lt;5mg/l). VDBP levels were determined by ELISA, and 25(OH)D by LCMS. Free and bioavailable vitamin D levels were calculated using the validated formula. IBM SPSS version 25.0 was used for statistical analysis. Results In total, 129 subjects with IBD (70 male/59 female; 82 CD/47 UC; mean age 41.7 ± 12.6 years) were enrolled. Of these, 38/129 had inflammation (19 m/19 f; 26 CD/12 UC; 39.6 ± 12.9 years) while 91/129 had no inflammation (40 m/51 f; 56 CD/35 UC; 42.5 ± 12.5 years). Subjects with disease activity had significantly higher leukocyte, erythrocyte sedimentation rate (ESR) and hsCRP, but lower transferrin, transferrin saturation (TSAT) and albumin levels than those without inflammation (p &lt; 0.05). Average serum levels of 25(OH)D (24.6[6.8–54.8] vs. 26.4[5.0–74.4]ng/ml), free 25(OH)D (5.9[1.3–13.3] vs. 1.0[1.0–21.4]ng/ml) and bioavailable 25(OH)D(2.3 [0.1–4.7] vs. 2.4[0.5–19.5]ng/ml) were similar in patients with vs. without inflammation (p &gt; 0.05). However, VDBP levels were significantly higher in inflammatory conditions (359.6[252.2–530.6] mg/l vs. 327.4[183.5–560.3]mg/l; p &lt; 0.05) and showed a positive correlation with CRP levels (0.293, p &lt; 0.001). Ratio of free/total 25(OH)D correlated negatively with CRP levels (−0.282, p = 0.002). Conclusion High levels of circulating VDBP were associated with inflammatory activity. Moreover, free/total 25(OH)D ratio was inversely associated with inflammation. Other vitamin D parameters including total, free and bioavailable 25(OH)D showed no association with inflammation. These findings suggest that VDBP may play a bigger role than thought as a modulator of vitamin D and inflammation, and that simultaneous detection and investigation of plasma VDBP may provide additional insights into this complex interaction.

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