Intestinal Calcium Transporter Genes Are Upregulated by Estrogens and the Reproductive Cycle Through Vitamin D Receptor-Independent Mechanisms

Cromphaut, Sophie J. Van; Rummens, Katrien; Stockmans, Ingrid; Herck, Erik Van; Dijcks, Fred A.; Ederveen, A. G. H.; Carmeliet, Peter; Verhaeghe, Johan; Bouillon, Roger; Carmeliet, Geert

doi:10.1359/jbmr.2003.18.10.1725

Cited by 206 publications

(163 citation statements)

References 60 publications

(131 reference statements)

Supporting

Mentioning

147

Contrasting

Unclassified

Order By: Relevance

“…This lack of age-dependent differences is in accordance with findings --gained with identical study design and methodology --in cattle and goat (Riner, 2006;Singer, 2006) and several other reports (Kinyamu et al, 1997;Wood et al, 1998;Lee et al, 2003;Pazianas et al, 2003;Yamagishi et al, 2006) and in contrast to data published elsewhere (Horst et al, 1990;Ebeling et al, 1992;Liang et al, 1994;Bischoff et al, 2001;Duque et al, 2002;Holick, 2003). Since an age and/or estrogen dependent impairment of calcium resorption was detectable in elder subjects in numerous studies, a resistance to vitamin D was postulated (Kinyamu et al, 1997;Wood et al, 1998) and furthermore vitamin D-dependent (Kinyamu et al, 1997;Liel et al, 1999;Schwartz et al, 2000;Leonard et al, 2001;Duque et al, 2002;Gilad et al, 2005) and independent effects of estrogens on calcium resorption were verified (Colin et al, 1999;Eisman, 2001;Van Cromphaut et al, 2003). Thus, in future studies hormone-and age-associated effects on calcium and vitamin D metabolism in sheep should be re-examined also in senescent dams with and without hormone substitution and evaluated separately.…”

Section: Resultsmentioning

confidence: 95%

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

Riner

Boos

Hässig

et al. 2007

Journal of Morphology

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 95%

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

Riner

Boos

Hässig

et al. 2007

Journal of Morphology

View full text Add to dashboard Cite

show abstract

“…The increased Ca absorption is thought to be the reason for the hypercalciuria that is observed during pregnancy. Some investigators have suggested that Ca absorption during pregnancy is not dependent on vitamin D, since intestinal Ca transport genes are up regulated by oestrogens, which are increased Proceedings of the Nutrition Society during pregnancy (5) . However, severe vitamin D deficiency with secondary hyperparathyroidism during pregnancy has been shown to lead to abnormal neonatal Ca homoeostasis.…”

Section: Fetal Ca Demands During Pregnancymentioning

confidence: 99%

Does vitamin D during pregnancy impact offspring growth and bone?

Specker

2011

Proc. Nutr. Soc.

View full text Add to dashboard Cite

During pregnancy, maternal and fetal Ca demands are met through increased intestinal Ca absorption. Increased Ca absorption may be more dependent on oestrogen's up-regulation of Ca transport genes than on vitamin D status. Numerous studies, however, have found that severe vitamin D deficiency with secondary hyperparathyroidism during pregnancy leads to abnormal Ca homoeostasis in the neonate. Some, but not all, studies of maternal vitamin D supplementation during pregnancy find a greater birth weight among infants of mothers with adequate vitamin D status. Observational studies find a higher incidence of small-for-gestational age (SGA) infants among mothers who are vitamin D deficient, but this effect may be modified by genetics. In addition, the effect of vitamin D status on SGA may not be linear, with increased occurrence of SGA at high maternal 25-hydroxyvitamin D (25-OHD) concentrations. Some studies, but not all, also have found that maternal vitamin D status is associated with growth trajectory during the first year of life, although the findings are contradictory. There are recent studies that suggest maternal 25-OHD, or surrogates of vitamin D status, are associated with growth and bone mass later in childhood. These results are not consistent, and blinded randomised trials of vitamin D supplementation during pregnancy with long-term follow-up are needed to determine the benefits, and possible risks, of maternal vitamin D status on offspring growth and bone development. The possibility of adverse outcomes with higher maternal 25-OHD concentrations should be considered and investigated in all ongoing and future studies. (2) . The increase in 1,25-(OH) 2 D concentrations is accompanied by an increase in intestinal Ca absorption, and fractional Ca absorption is approximately 50-60 % greater than pre-pregnant levels during the second and third trimesters (3,4) . The increased Ca absorption is thought to be the reason for the hypercalciuria that is observed during pregnancy. Some investigators have suggested that Ca absorption during pregnancy is not dependent on vitamin D, since intestinal Ca transport genes are up regulated by oestrogens, which are increased SGA, small-for-gestational age; UVB, ultraviolet B.

show abstract

“…Nonspecific blockage with ruthenium red, Gd 3+ , and La 3+ was observed (19). TRPV6 mRNA expression is regulated by dietary calcium, 1,25-vitamin D3, dihydrotestosterone, and estrogen (20)(21)(22). The intestinal calcium absorption is significantly reduced in TRPV6 knockout mice (23).…”

Section: Introductionmentioning

confidence: 97%

Tamoxifen Inhibits TRPV6 Activity via Estrogen Receptor–Independent Pathways in TRPV6-Expressing MCF-7 Breast Cancer Cells

Bolanz

Kovács

Landowski

et al. 2009

Molecular Cancer Research

View full text Add to dashboard Cite

The epithelial calcium channel TRPV6 is upregulated in breast carcinoma compared with normal mammary gland tissue. The selective estrogen receptor modulator tamoxifen is widely used in breast cancer therapy. Previously, we showed that tamoxifen inhibits calcium uptake in TRPV6-transfected Xenopus oocytes. In this study, we examined the effect of tamoxifen on TRPV6 function and intracellular calcium homeostasis in MCF-7 breast cancer cells transiently transfected with EYFP-C1-TRPV6. TRPV6 activity was measured with fluorescence microscopy using Fura-2. The basal calcium level was higher in transfected cells compared with nontransfected cells in calcium-containing solution but not in nominally calcium-free buffer. Basal influxes of calcium and barium were also increased. In transfected cells, 10 μmol/L tamoxifen reduced the basal intracellular calcium concentration to the basal calcium level of nontransfected cells. Tamoxifen decreased the transport rates of calcium and barium in transfected cells by 50%. This inhibitory effect was not blocked by the estrogen receptor antagonist, ICI 182,720. Similarly, a tamoxifen-induced inhibitory effect was also observed in MDA-MB-231 estrogen receptor-negative cells. The effect of tamoxifen was completely blocked by activation of protein kinase C. Inhibiting protein kinase C with calphostin C decreased TRPV6 activity but did not alter the effect of tamoxifen. These findings illustrate how tamoxifen might be effective in estrogen receptor-negative breast carcinomas and suggest that the therapeutic effect of tamoxifen and protein kinase C inhibitors used in breast cancer therapy might involve TRPV6-mediated calcium entry. This study highlights a possible role of TRPV6 as therapeutic target in breast cancer therapy.

show abstract

Intestinal Calcium Transporter Genes Are Upregulated by Estrogens and the Reproductive Cycle Through Vitamin D Receptor-Independent Mechanisms

Cited by 206 publications

References 60 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

Does vitamin D during pregnancy impact offspring growth and bone?

Tamoxifen Inhibits TRPV6 Activity via Estrogen Receptor–Independent Pathways in TRPV6-Expressing MCF-7 Breast Cancer Cells

Contact Info

Product

Resources

About