| Abstrakt: |
The epithelial Ca[sup 2+] channels TRPV5 and TRPV6 are localized to the brush border membrane of intestinal cells and constitute the postulated rate-limiting entry step of active Ca[sup 2+] absorption. The aim of the present study was to investigate the hormonal regulation of these channels. To this end, the effect of 17β-estradiol (17β-E[sub 2]), 1,25-dihydroxyvitamin D[sub 3] [1,25(OH)[sub 2]D[sub 3]], and dietary Ca[sup 2+] on the expression of the duodenal Ca[sup 2+] transport proteins was investigated in vivo and analyzed using real-time quantitative PCR. Supplementation with 17β-E[sub 2] increased duodenal gene expression of TRPV5 and TRPV6 but also calbindin-D[sub 9K] and plasma membrane Ca[sup 2+]-ATPase (PMCA1b) in ovariectomized rats. 25-Hydroxyvitamin D[sub 3]-1αhydroxylase (1α-OHase) knockout mice are characterized by hyperparathyroidism, rickets, hypocalcemia, and undetectable levels of 1,25(OH)[sub 2]D[sub 3] and were used to study the 1,25(OH)[sub 2]D[sub 3]-dependency of the stimulatory effects of 17β-E[sub 2]. Treatment with 17β-E[sub 2] upregulated mRNA levels of duodenal TRPV6 in these 1α-OHase knockout mice, which was accompanied by increased serum Ca[sup 2+] concentrations from 1.69 ± 0.10 to 2.03 ± 0.12 mM (P < 0.05). In addition, high dietary Ca[sup 2+] intake normalized serum Ca[sup 2+] in these mice and upregulated expression of genes encoding the duodenal Ca[sup 2+] transport proteins except for PMCA1b. Supplementation with 1,25(OH)[sub 2]D[sub 3] resulted in increased expression of TRPV6, calbindin-D[sub 9K], and PMCA1b and normalization of serum Ca[sup 2+]. Expression levels of duodenal TRPV5 mRNA are below detection limits in these 1α-OHase knockout mice, but supplementation with 1,25(OH)[sub 2]D[sub 3] upregulated the expression to significant levels. In conclusion, TRPV5 and TRPV6 are regulated by 17β-E[sub 2] and 1,25(OH)[sub 2]D[sub 3], whereas dietary Ca[sup... [ABSTRACT FROM AUTHOR] |
