|Reinhardt, Timothy - Tim|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 5/29/1997
Publication Date: N/A
Citation: Interpretive Summary:
Technical Abstract: The present experiments were conducted to compare the relative hypercalcuric and hypercalcemic activities of 1,24(OH)2D2, 1,24(OH)2D3, and 1,25(OH)2D3 in 7-week-old rats. The rats were dosed orally with each sterol for 7 days at a rate of 1ng/g BW/day. We also monitored the ability of these compounds to up-regulate the 24-hydroxylase mRNA and to evoke modifications in the VDR/RXR heterodimer conformation. Plasma calcium was elevated in the rats treated with 1,24(OH)2D3 and 1,25(OH)2D3, but not in the 1,24(OH)2D2-dosed rats. Urinary calcium was significantly elevated in all groups. The order of hypercalcuric activity was 1,25(OH)2D3 > 1,24(OH)2D3 > 1,24(OH)2D2. Duodenal 24-hydroxylase mRNA was elevated in all groups; however, the elevations were significantly higher in the 1,24(OH)2D3 and 1,25(OH)2D3 groups. Kidney 24-hydroxylase was also significantly elevated in 1,24(OH)2D3- and 1,25(OH)2D3- treated rats. Recombinant human VDR extracts were incubated with saturating concentrations of 1,24(OH)2D2 and 1,25(OH)2D3, and subsequently analyzed by EMSA.