The 3-epi- and 24-oxo-derivatives of 1α,25 dihydroxyvitamin D3 stimulate transcription through the vitamin D receptor

Messerlian, Serge; Gao, Xiangming; St‐Arnaud, René

doi:10.1016/s0960-0760(99)00148-x

Cited by 16 publications

(8 citation statements)

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“…Albeit not clearly understood, alternative metabolism of vitamin D via epimerisation to 3-epi-25(OH)D3 results in the formation of 3-epi-1,25(OH) 2 D3, which binds to VDR to activate target gene transcription. Importantly, 3-epi-1,25(OH) 2 D3 appears a less potent VDR agonist than 1,25(OH) 2 D3, which may have physiological consequences ( 48 ). In normal pregnancy, 3-epi-25(OH) 2 D3 appears directly linked to 25(OH)D3 concentrations ( 43 ); however, in the SCOPE cohort this relationship was lost only in those women who developed PET.…”

Section: Discussionmentioning

confidence: 99%

Serum and urine vitamin D metabolite analysis in early preeclampsia

Tamblyn

Jenkinson

Larner

et al. 2018

Endocrine Connections

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Vitamin D deficiency is common in pregnant women and may contribute to adverse events in pregnancy such as preeclampsia (PET). To date, studies of vitamin D and PET have focused primarily on serum concentrations vitamin D, 25-hydroxyvitamin D3 (25(OH)D3) later in pregnancy. The aim here was to determine whether a more comprehensive analysis of vitamin D metabolites earlier in pregnancy could provide predictors of PET. Using samples from the SCOPE pregnancy cohort, multiple vitamin D metabolites were quantified by liquid chromatography–tandem mass spectrometry in paired serum and urine prior to the onset of PET symptoms. Samples from 50 women at pregnancy week 15 were analysed, with 25 (50%) developing PET by the end of the pregnancy and 25 continuing with uncomplicated pregnancy. Paired serum and urine from non-pregnant women (n = 9) of reproductive age were also used as a control. Serum concentrations of 25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 24,25(OH)2D3 and 3-epi-25(OH)D3 were measured and showed no significant difference between women with uncomplicated pregnancies and those developing PET. As previously reported, serum 1,25(OH)2D3 was higher in all pregnant women (in the second trimester), but serum 25(OH)D2 was also higher compared to non-pregnant women. In urine, 25(OH)D3 and 24,25(OH)2D3 were quantifiable, with both metabolites demonstrating significantly lower (P < 0.05) concentrations of both of these metabolites in those destined to develop PET. These data indicate that analysis of urinary metabolites provides an additional insight into vitamin D and the kidney, with lower urinary 25(OH)D3 and 24,25(OH)2D3 excretion being an early indicator of a predisposition towards developing PET.

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Section: Discussionmentioning

confidence: 99%

Serum and urine vitamin D metabolite analysis in early preeclampsia

Tamblyn

Jenkinson

Larner

et al. 2018

Endocrine Connections

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“…Alternative metabolism of vitamin D may also occur via epimerisation of 25(OH)D3. The resulting 3- epi -25(OH)D3 can be converted to 3- epi -1,25(OH) 2 D3, and then bind to VDR to activate target gene transcription [36]. However, 3- epi -1,25(OH) 2 D3 is a much less potent VDR agonist than 1,25(OH) 2 D3, suggesting that epimerisation of 25(OH)D3 acts to dial-down VDR activity by generating a less effective ligand for the receptor [37].…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of maternal and placental vitamin D metabolism in preeclampsia

et al. 2017

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Introduction Epidemiology has linked preeclampsia (PET) to decreased maternal serum 25-hydroxyvitamin D3 (25(OH)D3). However, alterations in systemic and placental/decidual transport and metabolism of 25(OH)D3 during pregnancy suggest that other forms of vitamin D may also contribute to the pathophysiology of PET. Methods In a cross sectional analysis of normal pregnant women at 1st (n = 25) and 3rd trimester (n = 21), pregnant women with PET (n = 22), and non-pregnant female controls (n = 20) vitamin D metabolites were quantified in paired maternal serum, placental, and decidual tissue. Results Serum 25(OH)D3 was not significantly different in sera across all four groups. In normal 3rd trimester pregnant women serum active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was significantly higher than non-pregnant, normal 1st trimester pregnant, and PET women. Conversely, PET sera showed highest levels of the catabolites 3-epi-25(OH)D3 and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3). Serum albumin was significantly lower in normal 3rd trimester pregnant women and PET relative to normal 1st trimester pregnant women, but there was no change in free/bioavailable 25(OH)D3. In PET placental tissue, 25(OH)D3 and 3-epi-25(OH)D3 were lower than normal 3rd trimester tissue, whilst placental 24,25(OH)2D3 was highest in PET. Tissue 1,25(OH)2D3 was detectable in 1st trimester decidua, which also showed 10-fold higher 25(OH)D3 relative to paired placentae. 3-epi-25(OH)D3 and 24,25(OH)2D3 were not different for decidua and placenta. In normal 3rd trimester pregnant women, total, free and bioavailable maternal 25(OH)D3 correlated with placental 25(OH)D3, but this was not conserved for PET. Discussion These data indicate that PET is associated with decreased activation, increased catabolism, and impaired placental uptake of 25(OH)D3.

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“…The issue of the bioactivity of 1,25-OHD vs. that of 3-epi-1,25-OHD is more complex. 3-Epi-1,25-OHD can stimulate gene transcription through the vitamin D receptor (VDR) despite the fact that it appears to have weaker binding affinity to the VDR than 1,25-OHD (32,33). The lower receptor binding affinity does not translate into universally reduced biological effects of 3-epi-1,25-OHD in all vitamin-D-respon-sive tissues.…”

Section: Discussionmentioning

confidence: 99%