Expression of genes involved in calcium absorption in human duodenum

Walters, Julian R.F.; Howard,; Lowery,; Mawer,; Legon,

doi:10.1046/j.1365-2362.1999.00439.x

Cited by 39 publications

(33 citation statements)

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“…It may therefore be speculated that differentiation of post-mitotic cells to cells exhibiting above-average calcium absorbing capacities is correlated with above-average vitamin D receptor expression rates. Via vitamin D receptor mediated genomic mechanisms calcitriol should provide a calcium absorbing machinery of maximum capacity, i.e., high contents of calbindin-D9k (Haussler et al, 1995;Zhu et al, 1998;Walters et al, 1999;Christakos et al, 2003;Lee et al, 2003;Yamagishi et al, 2006), of its own receptor (Horst et al, 1990;Haussler et al, 1995;Chen et al, 2006;Yamagishi et al, 2006) and of Ca-transporting ATPase (Haussler et al, 1995;Zhu et al, 1998;Yamagishi et al, 2006) as already confirmed for some of these parameters in several studies (Feldman et al, 1979;Clemens et al, 1988;Lointier et al, 1991;Barley et al, 1999;Yamamoto et al, 1999;Barley et al, 2001;Yamagishi et al, 2002). Finally, the quantitative role of intestinal Ca absorption in domestic ruminants is discussed controversially because it was shown that the rumen is an important site for active and calbindin-9kD-independent Ca absorption in sheep (Schröder et al, 1997(Schröder et al, , 1999(Schröder et al, , 2001Wilkens, 2006;Leonhard-Marek et al, 2007;Schröder and Breves, 2007).…”

Section: Resultsmentioning

confidence: 99%

“…Expression of calbindin-D9k (Haussler et al, 1995;Zhu et al, 1998;Walters et al, 1999;Christakos et al, 2003;Lee et al, 2003;Yamagishi et al, 2006), of its own receptor (Horst et al, 1990;Haussler et al, 1995;Zhu et al, 1998;Chen et al, 2006;Yamagishi et al, 2006) and of Ca-transporting ATPase (CaATPase) (Haussler et al, 1995;Zhu et al, 1998;Yamagishi et al, 2006) are involved.…”

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Vitamin D receptor distribution in intestines of domesticated sheep Ovis ammon f. aries

Riner

Boos

Hässig

et al. 2007

Journal of Morphology

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The biologically active form of vitamin D, i.e., 1,25‐dihydroxycholecalciferol or calcitriol, plays an important role in bone metabolism and calcium homeostasis, which is often disturbed at the onset of lactation in high milk‐yielding domestic ruminants. Gene transcription is modulated via vitamin D receptors, but nongenomic effects of vitamin D via membrane receptors have also been described. In the intestines, vitamin D promotes calcium absorption via vitamin D receptors. Vitamin D receptors are of clinical relevance, but have not been systematically assessed within all segments of the intestine in any species. Thus, we present for the first time an immunohistochemical study of the distribution patterns of the vitamin D receptor protein in sheep, which may be the basis for present and future investigations on mineral homeostasis in domestic ruminants. Tissue probes of the intestines were collected from five lambs and five nonlactating and nonpregnant dams, fixed in formalin, embedded in paraffin, and used for the assessment of vitamin D receptor protein. Nuclear vitamin D receptor immunoreaction was scored semiquantitatively and exhibited a segment‐specific distribution pattern. Goblet cells always were devoid of any vitamin D receptor immunoreaction. Surface epithelial cells and enterocytes of the crypt openings generally demonstrated only a weak immunoreaction. Basally and/or intermediately located crypt epithelial cells exhibited stronger immunoreactions in duodenum, jejunum, and colon descendens. This basal/intermediate to superficial gradient was most pronounced in the duodenum and less evident in jejunum and colon descendens and not observed in ileum and cecum. There were no age‐dependent variations in vitamin D receptor protein expression. Results demonstrate that intestinal vitamin D receptor distribution patterns are segment‐specific and strongest immunoreactions correlate with highest intestinal calcium absorptive activities, as reported in literature. Strong expression of vitamin D receptors within the lower half of crypts also suggests a role for calcitriol in epithelial differentiation and cellular homeostasis. J. Morphol., 2008. © 2007 Wiley‐Liss, Inc.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Vitamin D receptor distribution in intestines of domesticated sheep Ovis ammon f. aries

Riner

Boos

Hässig

et al. 2007

Journal of Morphology

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“…Most of these effects are mediated through the binding of hormone to the nuclear vitamin D receptor (VDR) and enhanced transcription of its target genes. For example, in the small intestine, 1,25(OH) 2 D 3 stimulates the production of a calcium binding protein (calbindin-D9K) that facilitates the transcellular movement of calcium from the intestinal lumen into the blood (Kumar, 1990;Walters et al, 1999). This phenomenon constitutes an important component of a highly regulated and dynamic system to maintain blood and cellular calcium homeostasis (Issa et al, 1998).…”

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Intestinal and Hepatic CYP3A4 Catalyze Hydroxylation of 1α,25-Dihydroxyvitamin D₃: Implications for Drug-Induced Osteomalacia

et al. 2005

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The decline in bone mineral density that occurs after longterm treatment with some antiepileptic drugs is thought to be mediated by increased vitamin D 3 metabolism. In this study, we show that the inducible enzyme CYP3A4 is a major source of oxidative metabolism of 1␣,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] in human liver and small intestine and could contribute to this adverse effect. Heterologously-expressed CYP3A4 catalyzed the 23-and 24-hydroxylation of 1,25(OH) 2 D 3 . No human microsomal cytochrome P450 enzyme tested, other than CYP3A5, supported these reactions. CYP3A4 exhibited opposite product stereochemical preference compared with that of CYP24A1, a known 1,25(OH) 2 D 3 hydroxylase. The three major metabolites generated by CYP3A4 were 1,23R,25(OH) 3 D 3 , 1,24S,25(OH) 3 D 3 , and 1,23S,25(OH) 3 D 3 . Although the metabolic clearance of CYP3A4 was less than that of CYP24A1, comparison of metabolite profiles and experiments using CYP3A-specific inhibitors indicated that CYP3A4 was the dominant source of 1,25(OH) 2 D 3 23-and 24-hydroxylase activity in both human small intestine and liver. Consistent with this observation, analysis of mRNA isolated from human intestine and liver (including samples from donors treated with phenytoin) revealed a general absence of CYP24A1 mRNA. In addition, expression of CYP3A4 mRNA in a panel of duodenal samples was significantly correlated with the mRNA level of a known vitamin D receptor gene target, calbindin-D9K. These and other data suggest that induction of CYP3A4-dependent 1,25(OH) 2 D 3 metabolism by antiepileptic drugs and other PXR ligands may diminish intestinal effects of the hormone and contribute to osteomalacia.

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“…18,19) In humans, 1,25-(OH) 2 D 3 up-regulates the expression of calbindin-D9k which facilitates intracellular calcium diffusion across intestinal epithelial cells. 20) The expression of CaT1 in Caco-2 cells has also been reported to be enhanced by 1,25-(OH) 2 D 3 , 15,21,22) whereas the expression of CaT1 in the human duodenum was not.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the Intestinal Ca²⁺Uptake by a Cheese Whey Protein Digest

Takano

Matsuura

Yoshikawa

et al. 2007

Bioscience, Biotechnology, and Biochemistry

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Expression of genes involved in calcium absorption in human duodenum

Abstract: In normal humans, 1, 25-dihydroxycholecalciferol has a small but significant relationship to duodenal expression of calbindin-D9k, but not to PMCA1 expression.

Cited by 39 publications

References 49 publications

Vitamin D receptor distribution in intestines of domesticated sheep Ovis ammon f. aries

Vitamin D receptor distribution in intestines of domesticated sheep Ovis ammon f. aries

Intestinal and Hepatic CYP3A4 Catalyze Hydroxylation of 1α,25-Dihydroxyvitamin D₃: Implications for Drug-Induced Osteomalacia

Modulation of the Intestinal Ca²⁺Uptake by a Cheese Whey Protein Digest

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Expression of genes involved in calcium absorption in human duodenum

Abstract: In normal humans, 1, 25-dihydroxycholecalciferol has a small but significant relationship to duodenal expression of calbindin-D9k, but not to PMCA1 expression.

Cited by 39 publications

References 49 publications

Vitamin D receptor distribution in intestines of domesticated sheep Ovis ammon f. aries

Vitamin D receptor distribution in intestines of domesticated sheep Ovis ammon f. aries

Intestinal and Hepatic CYP3A4 Catalyze Hydroxylation of 1α,25-Dihydroxyvitamin D3: Implications for Drug-Induced Osteomalacia

Modulation of the Intestinal Ca2+Uptake by a Cheese Whey Protein Digest

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Intestinal and Hepatic CYP3A4 Catalyze Hydroxylation of 1α,25-Dihydroxyvitamin D₃: Implications for Drug-Induced Osteomalacia

Modulation of the Intestinal Ca²⁺Uptake by a Cheese Whey Protein Digest