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Intestinal calcium transporter genes are upregulated by estrogens and the reproductive cycle through vitamin D receptor-independent mechanisms.
J Bone Miner Res 2003; 18(10):1725-36JB

Abstract

1alpha,25(OH)2-vitamin D strongly regulates the expression of the epithelial calcium channel CaT1. CaT1 expression is reduced in ERKOalpha mice and induced by estrogen treatment, pregnancy, or lactation in VDR WT and KO mice. Estrogens and vitamin D are thus independent potent regulators of the expression of this calcium influx mechanism, which is involved in active intestinal calcium absorption.

INTRODUCTION

Active duodenal calcium absorption consists of three major steps: calcium influx into, transfer through, and extrusion out of the enterocyte. These steps are carried out by the calcium transport protein 1 (CaT1), calbindin-D9K, and the plasma membrane calcium ATPase (PMCA1b), respectively. We investigated whether estrogens or hormonal changes during the female reproductive cycle influence the expression of these genes, and if so, whether these effects are vitamin D-vitamin D receptor (VDR) dependent.

MATERIALS AND METHODS

We evaluated duodenal expression patterns in estrogen receptor (ER)alpha and -beta knockout (KO) mice, as well as in ovariectomized, estrogen-treated, pregnant, and lactating VDR wild-type (WT) and VDR KO mice.

RESULTS

Expression of calcium transporter genes was not altered in ERKObeta mice. CaT1 mRNA expression was reduced by 55% in ERKOalpha mice, while the two other calcium transporter genes were not affected. Ovariectomy caused no change in duodenal expression pattern of VDR WT and KO mice, whereas treatment with a pharmacologic dose of estrogens induced CaT1 mRNA expression in VDR WT (4-fold) and KO (8-fold) mice. Pregnancy enhanced CaTI expression equally in VDR WT and KO mice (12-fold). Calbindin-D9K and PMCA1b expression increased to a lesser extent and solely in pregnant VDR WT animals. In lactating VDR WT and KO mice, CaT1 mRNA expression increased 13 times, which was associated with a smaller increase in calbindin-D9K protein content and PMCA1b mRNA expression.

CONCLUSIONS

Estrogens or hormonal changes during pregnancy or lactation have distinct, vitamin D-independent effects at the genomic level on active duodenal calcium absorption mechanisms, mainly through a major upregulation of the calcium influx channel CaT1. The estrogen effects seem to be mediated solely by ERalpha.

Authors+Show Affiliations

Laboratory of Experimental Medicine and Endocrinology (Legendo), Katholieke Universiteit Leuven, Leuven, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14584880

Citation

Van Cromphaut, S J., et al. "Intestinal Calcium Transporter Genes Are Upregulated By Estrogens and the Reproductive Cycle Through Vitamin D Receptor-independent Mechanisms." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 18, no. 10, 2003, pp. 1725-36.
Van Cromphaut SJ, Rummens K, Stockmans I, et al. Intestinal calcium transporter genes are upregulated by estrogens and the reproductive cycle through vitamin D receptor-independent mechanisms. J Bone Miner Res. 2003;18(10):1725-36.
Van Cromphaut, S. J., Rummens, K., Stockmans, I., Van Herck, E., Dijcks, F. A., Ederveen, A. G., ... Carmeliet, G. (2003). Intestinal calcium transporter genes are upregulated by estrogens and the reproductive cycle through vitamin D receptor-independent mechanisms. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 18(10), pp. 1725-36.
Van Cromphaut SJ, et al. Intestinal Calcium Transporter Genes Are Upregulated By Estrogens and the Reproductive Cycle Through Vitamin D Receptor-independent Mechanisms. J Bone Miner Res. 2003;18(10):1725-36. PubMed PMID: 14584880.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intestinal calcium transporter genes are upregulated by estrogens and the reproductive cycle through vitamin D receptor-independent mechanisms. AU - Van Cromphaut,S J, AU - Rummens,K, AU - Stockmans,I, AU - Van Herck,E, AU - Dijcks,F A, AU - Ederveen,A G H, AU - Carmeliet,P, AU - Verhaeghe,J, AU - Bouillon,R, AU - Carmeliet,G, PY - 2003/10/31/pubmed PY - 2004/6/3/medline PY - 2003/10/31/entrez SP - 1725 EP - 36 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J. Bone Miner. Res. VL - 18 IS - 10 N2 - UNLABELLED: 1alpha,25(OH)2-vitamin D strongly regulates the expression of the epithelial calcium channel CaT1. CaT1 expression is reduced in ERKOalpha mice and induced by estrogen treatment, pregnancy, or lactation in VDR WT and KO mice. Estrogens and vitamin D are thus independent potent regulators of the expression of this calcium influx mechanism, which is involved in active intestinal calcium absorption. INTRODUCTION: Active duodenal calcium absorption consists of three major steps: calcium influx into, transfer through, and extrusion out of the enterocyte. These steps are carried out by the calcium transport protein 1 (CaT1), calbindin-D9K, and the plasma membrane calcium ATPase (PMCA1b), respectively. We investigated whether estrogens or hormonal changes during the female reproductive cycle influence the expression of these genes, and if so, whether these effects are vitamin D-vitamin D receptor (VDR) dependent. MATERIALS AND METHODS: We evaluated duodenal expression patterns in estrogen receptor (ER)alpha and -beta knockout (KO) mice, as well as in ovariectomized, estrogen-treated, pregnant, and lactating VDR wild-type (WT) and VDR KO mice. RESULTS: Expression of calcium transporter genes was not altered in ERKObeta mice. CaT1 mRNA expression was reduced by 55% in ERKOalpha mice, while the two other calcium transporter genes were not affected. Ovariectomy caused no change in duodenal expression pattern of VDR WT and KO mice, whereas treatment with a pharmacologic dose of estrogens induced CaT1 mRNA expression in VDR WT (4-fold) and KO (8-fold) mice. Pregnancy enhanced CaTI expression equally in VDR WT and KO mice (12-fold). Calbindin-D9K and PMCA1b expression increased to a lesser extent and solely in pregnant VDR WT animals. In lactating VDR WT and KO mice, CaT1 mRNA expression increased 13 times, which was associated with a smaller increase in calbindin-D9K protein content and PMCA1b mRNA expression. CONCLUSIONS: Estrogens or hormonal changes during pregnancy or lactation have distinct, vitamin D-independent effects at the genomic level on active duodenal calcium absorption mechanisms, mainly through a major upregulation of the calcium influx channel CaT1. The estrogen effects seem to be mediated solely by ERalpha. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/14584880/Intestinal_calcium_transporter_genes_are_upregulated_by_estrogens_and_the_reproductive_cycle_through_vitamin_D_receptor_independent_mechanisms_ L2 - https://doi.org/10.1359/jbmr.2003.18.10.1725 DB - PRIME DP - Unbound Medicine ER -