Stimulation of murine intestinal secretion by daily genistein injections: gender-dependent differences

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), μA/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.

Injecting with 600G elicited significant increases in basal I(sc) in females after 1-week (ñ70 μA/cm(2), n=15, p < 0.05) and in males after 2-weeks (ñ80 μA/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 μM) I(sc) was significantly inhibited by the CFTR chloride channel inhibitors, glibenclamide (500 μM) and CFTR(inh)-172 (100 μM) 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).

These data suggest that male and female mice both exhibit increased Cl- secretion with 600G, however, the mechanisms mediating this are gender-dependent.