No synergy between FXR and LRH-1 in human SHP regulation.

LRH-1 dose-dependently induced activation of the −303/+10 hSHP promoter fragment, confirming the presence of a functional LRH-1. In the presence of FXR a similar dose response curve is observed. However, in the presence of CDCA, FXR and LRH-1 do not synergistically activate the SHP promoter. LRH-1 rather limits the FXR/CDCA-dependent activation at a higher dose. DLD-1 cells were transfected with hFXR and hRXRα expression plasmids, the −303/+10 hSHP promoter construct and/or increasing amounts of an mLrh-1 expression plasmid as indicated. Cells were treated with or without 100 µmol/L CDCA. Luciferase activity was measured to determine the SHP promoter activity. a) significantly different from 0 ng mLrh-1 vehicle, between vehicle treated conditions. b) significantly different from 0 ng mLrh-1 FXR/RXRα, between FXR/RXRα treated conditions. Data presented as means ± SD; n≥3. P≤0.05 for a) and b) in a pairwise comparison by Mann-Whitney U test.