Stimulation of Murine Intestinal Secretion by Daily Genistein Injections: Gender-dependent Differences

Background/Aims: The effect of daily injections with genistein (naturally occurring phytoestrogen) on intestinal chloride (Cl-) secretion was measured with Ussing chamber short circuit current (I-sc, mu A/cm(2)), in C57BL/6J male and female mice, using 600 mg/kg genistein/day (600G), 300 mg/kg genistein/day (300G), 150 mg/kg genistein/day (150G) or genistein-free vehicle control (0G) for 1- or 2-weeks. Methods and Results: Injecting with 600G elicited significant increases in basal I-sc in females after 1-week (similar to 70 mu A/cm(2), n=15, p<0.05) and in males after 2-weeks (similar to 80 mu A/cm(2), n=5, p<0.05) compared to their 0G counterparts. Chloride-free ringer significantly reduced basal I-sc by 65% in 600G males and 72% in 600G females, suggesting that Cl-was the major anion comprising the genistein-stimulated secretion. The forskolin-stimulated (10 mu M) I-sc was significantly inhibited by the CFTR chloride channel inhibitors, glibenclamide (500 mu M) and CFTRinh-172 (100 mu M) in 600G males and females, suggesting some contribution by genistein-dependent CFTR-mediated Cl- secretion. We found no associated changes in intestinal morphology, nor change in total CFTR protein with 600G. There was a 5% increase in apical/subapical ratio in 600G males compared to controls (no change in females). Conclusion: These data suggest that male and female mice both exhibit increased Cl-secretion with 600G, however, the mechanisms mediating this are gender-dependent. Copyright (C) 2011 S. Karger AG, Basel