Morphologic effects of epithelial ion channels on the mouse uterus: differences between raloxifene analog (LY117018) and estradiol treatments.

OBJECTIVE: Estrogen regulates the expression of epithelial Na(+) channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR). Our purpose was to assess the effects of raloxifene analog LY117018 on the expression of ENaC and CFTR in ovariectomized mice. STUDY DESIGN: Three groups of 5 female ovariectomized mice were treated with 17beta-estradiol benzoate (E2), LY117018 (LY), or vehicle, respectively, for 4-12 weeks. Effects on the messenger ribonucleic acid expression levels of ENaC and CFTR channels in the uterus were studied using real-time reverse transcriptase-polymerase chain reaction. RESULTS: E2 treatment induced CFTR expression, repressed ENaC expression and resulted in fluid accumulation in the uterus. In contrast, LY induced CFTR expression, did not repress ENaC expression, and caused no fluid accumulation. CONCLUSION: Estradiol and LY117018 differentially regulate the expression of CFTR and ENaC in ovariectomized mouse uterus. This finding suggests that uterine fluid accumulation can be controlled mainly by targeting the ENaC.