scholarly journals Intestinal Resistance to 1,25 Dihydroxyvitamin D in Mice Heterozygous for the Vitamin D Receptor Knockout Allele

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1396-1402 ◽  
Author(s):  
Yurong Song ◽  
James C. Fleet

We tested the hypothesis that low vitamin D receptor (VDR) level causes intestinal vitamin D resistance and intestinal calcium (Ca) malabsorption. To do so, we examined vitamin D regulated duodenal Ca absorption and gene expression [transient receptor potential channel, vallinoid subfamily member 6 (TRPV6), 24-hydroxylase, calbindin D9k (CaBP) mRNA, and CaBP protein] in wild-type mice and mice with reduced tissue VDR levels [i.e. heterozygotes for the VDR gene knockout (HT)]. Induction of 24-hydroxylase mRNA levels by 1,25 dihydroxyvitamin D3 [1,25(OH)2 D3] injection was significantly reduced in the duodenum and kidney of HT mice in both time-course and dose-response experiments. TRPV6 and CaBP mRNA levels in duodenum were significantly induced after 1,25(OH)2 D3 injection, but there was no difference in response between wild-type and HT mice. Feeding a low-calcium diet for 1 wk increased plasma PTH, renal 1α-hydroxylase (CYP27B1) mRNA level, and plasma 1,25(OH)2 D3, and this response was greater in HT mice (by 88, 55, and 37% higher, respectively). In contrast, duodenal TRPV6 and CaBP mRNA were not higher in HT mice fed the low-calcium diet. However, the response of duodenal Ca absorption and CaBP protein to increasing 1,25(OH)2 D3 levels was blunted by 40% in HT mice. Our data show that low VDR levels lead to resistance of intestinal Ca absorption to 1,25(OH)2 D3, and this resistance may be due to a role for the VDR (and VDR level) in the translation of CaBP.

1981 ◽  
Vol 64 (2) ◽  
pp. 217-226 ◽  
Author(s):  
H.B. Green ◽  
R.L. Horst ◽  
D.C. Beitz ◽  
E.T. Littledike

1974 ◽  
Vol 52 (5) ◽  
pp. 972-977
Author(s):  
Claude L. Morin ◽  
Jean Léveillé ◽  
Victor Ling

Generalized hyperaminoaciduria and hyperphosphaturia are associated with human vitamin D deficiency rickets and the effect has been reproduced in animals. The basis for the renal transport impairment was attributed to secondary hyperparathyroidism resulting from hypocalcemia.In this study we attempted over a 16-week period to induce hyperaminoaciduria in Holtzman rats with vitamin D deficient diets of varying calcium content (0.4% and 0.04%) so as to investigate the possibility of a concomitant defect in intestinal transport of amino acids. Despite signs of secondary hyperparathyroidism, generalized hyperaminoaciduria was not in evidence in any of the groups. However, increased urinary excretion of lysine and taurine was demonstrated in rats fed a low calcium diet without vitamin D (LCa−D). The same observation was also made for taurine in rats deprived of vitamin D and on a normal calcium diet (NCa−D) and in animals fed a low calcium diet with vitamin D (LCa+D). The results failed to show any effect of vitamin D deficiency, hypocalcemia, or secondary hyperparathyroidism on the intestinal transport of lysine, alanine, and cycloleucine.


1999 ◽  
Vol 255 (3) ◽  
pp. 731-734 ◽  
Author(s):  
H.J. Armbrecht ◽  
T.L. Hodam ◽  
M.A. Boltz ◽  
V.B. Kumar

2008 ◽  
Vol 23 (8) ◽  
pp. 2563-2570 ◽  
Author(s):  
A. Pasch ◽  
F. J. Frey ◽  
U. Eisenberger ◽  
M. G. Mohaupt ◽  
O. Bonny

1965 ◽  
Vol 65 (1) ◽  
pp. 15-19 ◽  
Author(s):  
M. R. McRoberts ◽  
R. Hill ◽  
A. C. Dalgarno

1. The teeth of sheep that had been fed from 6 months of age for 12 months on diets low in calcium or in phosphorus and vitamin D content were compared with those of similar animals fed a control diet.2. The low calcium diet depressed the development of both dentine and enamel but had a greater effect on enamel than dentine, while the low phosphorus and vitamin D diet depressed dentine development slightly and had practically no effect on enamel.3. The percentages of ash of the dentine and enamel were not significantly affected by the diets fed.


1965 ◽  
Vol 65 (1) ◽  
pp. 11-14 ◽  
Author(s):  
M. R. McRoberts ◽  
R. Hill ◽  
A. C. Dalgarno

1. In growing sheep fed on a low-calcium diet for 12 months and for a similar period on a diet of adequate mineral content, a tendency for the incisor teeth to protrude beyond the maxillary pad (prognathism) was observed. This arose primarily during the repair period, and was apparently caused by poorer repair of the upper skull than of the mandible. This was not observed in animals fed on a control diet or one deficient in phosphorus and vitamin D.2. A malocclusion of molar teeth associated with poorly mineralized and extremely weak mandibles, which prevented the incisor teeth from meeting the dental pad, occurred in growing sheep fed for 12 months on a diet deficient in phosphorus and vitamin D. This defect was not observed in similar animals fed on a control diet nor in those fed on a diet of low calcium content. Treatment effects on the shape of the mandible that were apparently related to this malocclusion are described.


2004 ◽  
Vol 287 (1) ◽  
pp. F39-F47 ◽  
Author(s):  
Hiroko Segawa ◽  
Ichiro Kaneko ◽  
Setsuko Yamanaka ◽  
Mikiko Ito ◽  
Masahi Kuwahata ◽  
...  

Recent studies suggest that vitamin D may play a role in intestinal Na+-dependent phosphate transport adaptation to variable levels of dietary Pi. Therefore, the goal of the current study was to assess Na+-dependent Pi cotransport activity in transgenic mice to determine whether vitamin D is an essential mediator of this process. Intestinal brush-border membrane (BBM), Na+-dependent Pi cotransport activity was significantly decreased in vitamin D receptor (VDR) null [VDR (−/−)] mice compared with wild-type (VDR+/+) mice. While intestinal Na-Pi cotransporter (type IIb) mRNA levels were similar in VDR (−/−) and VDR (+/+) mice, type IIb Na-Pi cotransporter protein expression was markedly suppressed in VDR (−/−) mice compared with VDR (+/+) mice. Furthermore, Na-Pi cotransport activity in renal BBM was similar in VDR (−/−) and VDR (+/+) mice, but type IIa Na-Pi cotransporter protein expression was decreased in VDR (−/−) mice. After administration of a low-Pi diet, type IIb protein expression was significantly increased in VDR (+/+) and VDR (−/−) mice, and type IIb protein expression was present in the intestinal BBM of VDR (−/−) mice. These data demonstrate that intestinal Na-Pi cotransport adaptation to a low-Pi diet occurs independently of vitamin D.


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