Effects of one-year treatment with estrogens on bone mass, intestinal calcium absorption, and 25-hydroxyvitamin D-1α-hydroxylase reserve in postmenopausal osteoporosis

Civitelli, Roberto; Agnusdei, D.; Nardi, Paolo; Zacchei, F; Avioli, Louis V.; Gennari, C

doi:10.1007/bf02556338

Cited by 157 publications

(70 citation statements)

References 61 publications

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“…With the use of cultured opossum kidney cells, a suppressive effect of 17␤-E 2 on 1␣-OHase activity was demonstrated (33). Among postmenopausal women, however, estrogen replacement therapy resulted in unchanged or increased renal 1␣-OHase activity (30,34 (20,29,36,37). In contrast, some studies suggested a direct effect of 17␤-E 2 on Ca 2ϩ reabsorption, independent of vitamin D (3,28).…”

Section: Discussionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D3-Independent Stimulatory Effect of Estrogen on the Expression of ECaC1 in the Kidney

Abel¹,

Hoenderop²,

Dardenne

et al. 2002

Journal of the American Society of Nephrology

136

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Abstract. Estrogen deficiency results in a negative Ca 2ϩ balance and bone loss in postmenopausal women. In addition to bone, the intestine and kidney are potential sites for estrogen action and are involved in Ca 2ϩ handling and regulation. The epithelial Ca 2ϩ channel ECaC1 (or TRPV5) is the entry channel involved in active Ca 2ϩ transport. Ca 2ϩ entry is followed by cytosolic diffusion, facilitated by calbindin-D 28K and/or calbindin-D 9k , and active extrusion across the basolateral membrane by the Na ϩ /Ca 2ϩ -exchanger (NCX1) and plasma membrane Ca 2ϩ -ATPase (PMCA1b). In this transcellular Ca 2ϩ transport, ECaC1 probably represents the final regulatory target for hormonal control. The aim of this study was to determine whether 17␤-estradiol (17␤-E 2 ) is involved in Ca 2ϩ reabsorption via regulation of the expression of ECaC1. The ovariectomized rat model was used to investigate the regulation of ECaC1, at the mRNA and protein levels, by 17␤-E 2 replacement therapy. Using real-time quantitative PCR and immunohistochemical analyses, this study demonstrated that 17␤-E 2 treatment at pharmacologic doses increased renal mRNA levels of ECaC1, calbindin-D 28K , NCX1, and PMCA1b and increased the protein abundance of ECaC1. Furthermore, the involvement of 1,25-dihydroxyvitamin D 3 in the effects of 17␤-E 2 was examined in 25-hydroxyvitamin D 3 -1␣-hydroxylase-knockout mice. Renal mRNA expression of calbindin-D 9K , calbindin-D 28K , NCX1, and PMCA1b was not significantly altered after 17␤-E 2 treatment. In contrast, ECaC1 mRNA and protein levels were both significantly upregulated. Moreover, 17␤-E 2 treatment partially restored serum Ca 2ϩ levels, from 1.63 Ϯ 0.06 to 2.03 Ϯ 0.12 mM. In conclusion, this study suggests that 17␤-E 2 is positively involved in renal Ca 2ϩ reabsorption via the upregulation of ECaC1, an effect independent of 1,25-dihydroxyvitamin D 3 .

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Section: Discussionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D3-Independent Stimulatory Effect of Estrogen on the Expression of ECaC1 in the Kidney

Abel¹,

Hoenderop²,

Dardenne

et al. 2002

Journal of the American Society of Nephrology

136

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“…In this regard, available data indicate that decreased basal levels of 1,25(OH) 2 D 3 cannot solely account for the decrease in calcium absorption (Francis et al 1984), suggesting that the intestines of estrogen-depleted elderly or ovariectomized women are resistant to 1,25(OH) 2 D 3 (Gennari et al 1990). In addition, E2 administration has been shown to effectively restore the normal responsiveness of the intestine to 1,25(OH) 2 D 3 in ovariectomized pre- (Gennari et al 1990) and postmenopausal (Civitelli et al 1988, Heaney et al 1978 women.…”

Section: Introductionmentioning

confidence: 99%

Regulation of vitamin D receptor expression via estrogen-induced activation of the ERK 1/2 signaling pathway in colon and breast cancer cells

Gilad

Bresler²,

J³

et al. 2005

Journal of Endocrinology

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We previously demonstrated that 17 -estradiol (E2) regulates the transcription and expression of the vitamin D receptor (VDR) in rat colonocytes and duodenocytes in vivo. The aim of the present study was to assess whether the extracellular signal-regulated kinase (ERK) induced by E2 is involved in regulating VDR expression. We compared E2-associated signaling activity in HT29 colon cancer cells, a non-classical E2-target, with that in MCF-7 breast cancer cells, the natural targets of the hormone. E2 did not affect proliferation of HT29 cells, but enhanced proliferation of MCF-7 cells. Vitamin D inhibited proliferation of both cell lines and the combined treatment induced potentiation of vitamin D activity. E2 upregulated VDR transcription and protein expression concomitantly with ERK 1/2 phosphorylation in both cell lines. PD98059, a specific mitogen-activated protein kinase (MAPK) inhibitor, prevented E2-mediated activation of ERK 1/2, with concomitant inhibition of VDR expression. ICI182780 inhibited VDR expression in HT29 and MCF-7 cell lines. A conjugate of E2 and bovine serum albumin upregulated phosphorylation of ERK 1/2 and concomitantly enhanced VDR expression in a similar fashion as the nonconjugated hormone. Expression of ER and ER was detected in MCF-7 and HT29 cell lines respectively, which localized to the nuclei, cytosol and caveolar membrane rather than non-caveolar membrane. Disruption of lipid rafts/caveolae by depleting cellular cholesterol with the cholesterol-binding reagentmethylcyclodextrin blocked ERK 1/2 phosphorylation concomitantly with VDR upregulation. The tyrosine phosphorylation inhibitor suramin and src kinase inhibitor PP2 inhibited both ERK 1/2 phosphorylation and VDR expression. E2 induced phosphorylation of Raf and Jun in a time-dependent manner. The Ras/Raf dependent inhibitor of transactivation sulindac sulfide also blocked E2 effects. The specific c-Jun phosphorylation inhibitor SP600125 dose dependently inhibited c-Jun phosphorylation and VDR expression. The MAPK/ERK kinase inhibitor PD 98059 downregulated both c-Jun phosphorylation and VDR expression indicating that upstream and downstream events in the signaling cascade are all related to the control of VDR expression. Taken together, our data suggest that E2 binds to receptors compartmentalized to membranal caveolar domains in HT29 and MCF-7 cells, inducing ERK 1/2 activation and transcriptional activity, which finally results in upregulation of expression of the VDR gene.

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“…Estradiol replacement also prevented intestinal tumorigenesis and ameliorated enterocyte migration and intercellular adhesion in the Apc Min−/+ colorectal carcinoma mouse model (18). Furthermore, estrogen increases expression of VDR in rat intestine (19,20) and estrogen administration restores the responsiveness of the intestine to 1,25-dihydroxyvitamin D [1,25(OH 2 )D] in ovariectomized premenopausal (21) and postmenopausal women (22). Other tissues and cell systems, such as uterus (23), liver (24), and breast cancer cells (25), also respond to estradiol by increased VDR expression.…”

mentioning

confidence: 99%

Chemoprevention of Colorectal Neoplasia by Estrogen: Potential Role of Vitamin D Activity

Protiva

Cross

Hopkins

et al. 2009

Cancer Prevention Research

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Postmenopausal hormone replacement therapy lowers colon cancer incidence. In humans, the mechanism is unknown, but animal models suggest that it may involve activation of the vitamin D receptor (VDR) pathway.The aims of our study were to determine whether estrogen intervention affects global gene expression in rectal mucosal biopsies and whether vitamin D-related genes are affected.Estradiol was given to raise serum estradiol to premenopausal levels in 10 postmenopausal women under close nutritional control. Primary end points were expression of VDR, CYP24A1, CYP27B1, and E-cadherin in rectal mucosa by reverse transcription-PCR and examining response to estradiol by genome-wide arrays. Responses in gene expression in rectal biopsies to estrogen were determined in each subject individually and compared with a human estrogen response gene array database and a custom array in vitro-generated database.Cluster analysis showed that subjects maintained their overall gene expression profile and that interindividual differences were greater than intraindividual differences after intervention. Eight of 10 subjects showed significant enrichment in estrogen-responsive genes. Gene array group analysis showed activation of the VDR pathway and down-regulation of inflammatory and immune signaling pathways. Reverse transcription-PCR analysis showed significant up-regulation of VDR and E-cadherin, a downstream target of vitamin D action.These data suggest that the chemopreventive action of hormone replacement therapy on colon neoplasia results, at least in part, from changes in vitamin D activity. Evaluation of gene arrays is useful in chemopreventive intervention studies in small groups of subjects.

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Effects of one-year treatment with estrogens on bone mass, intestinal calcium absorption, and 25-hydroxyvitamin D-1α-hydroxylase reserve in postmenopausal osteoporosis

Cited by 157 publications

References 61 publications

1,25-Dihydroxyvitamin D3-Independent Stimulatory Effect of Estrogen on the Expression of ECaC1 in the Kidney

1,25-Dihydroxyvitamin D3-Independent Stimulatory Effect of Estrogen on the Expression of ECaC1 in the Kidney

Regulation of vitamin D receptor expression via estrogen-induced activation of the ERK 1/2 signaling pathway in colon and breast cancer cells

Chemoprevention of Colorectal Neoplasia by Estrogen: Potential Role of Vitamin D Activity

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