1,25-dihydroxyvitamin D(3)-independent stimulatory effect of estrogen on the expression of ECaC1 in the kidney.
SourceJournal of the American Society of Nephrology, 13, 8, (2002), pp. 2102-2109
Article / Letter to editor
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Journal of the American Society of Nephrology
SubjectRegulation of salt and water reabsorption in the renal collecting duct; Regulatie water en zouttransport in de verzamelbuis van de nier
Estrogen deficiency results in a negative Ca(2+) 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(2+) handling and regulation. The epithelial Ca(2+) channel ECaC1 (or TRPV5) is the entry channel involved in active Ca(2+) transport. Ca(2+) 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(+)/Ca(2+)-exchanger (NCX1) and plasma membrane Ca(2+)-ATPase (PMCA1b). In this transcellular Ca(2+) transport, ECaC1 probably represents the final regulatory target for hormonal control. The aim of this study was to determine whether 17beta-estradiol (17beta-E(2)) is involved in Ca(2+) 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 17beta-E(2) replacement therapy. Using real-time quantitative PCR and immunohistochemical analyses, this study demonstrated that 17beta-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 17beta-E(2) was examined in 25-hydroxyvitamin D(3)-1alpha-hydroxylase-knockout mice. Renal mRNA expression of calbindin-D(9K), calbindin-D(28K), NCX1, and PMCA1b was not significantly altered after 17beta-E(2) treatment. In contrast, ECaC1 mRNA and protein levels were both significantly upregulated. Moreover, 17beta-E(2) treatment partially restored serum Ca(2+) levels, from 1.63 +/- 0.06 to 2.03 +/- 0.12 mM. In conclusion, this study suggests that 17beta-E(2) is positively involved in renal Ca(2+) reabsorption via the upregulation of ECaC1, an effect independent of 1,25-dihydroxyvitamin D(3).
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