title: Stimulation of murine intestinal secretion by daily genistein injections: gender-dependent differences.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  These data suggest that male and female mice both exhibit increased Cl- secretion with 600G, however, the mechanisms mediating this are gender-dependent.
authors.affiliation: Department of Physiology, Midwestern University, Glendale, AZ 85308, USA. lalnak@midwestern.edu
authors.forename: Layla
authors.initials: L
authors.lastname: Al-Nakkash
authors.forename: Lyn
authors.initials: L
authors.lastname: Batia
authors.forename: Minoti
authors.initials: M
authors.lastname: Bhakta
authors.forename: Amity
authors.initials: A
authors.lastname: Peterson
authors.forename: Nathan
authors.initials: N
authors.lastname: Hale
authors.forename: Ryan
authors.initials: R
authors.lastname: Skinner
authors.forename: Steven
authors.initials: S
authors.lastname: Sears
authors.forename: Jesse
authors.initials: J
authors.lastname: Jensen
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D019833:Genistein / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012737:Sex Factors
chemical_list: D016588:Anticarcinogenic Agents; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D019833:Genistein; D005905:Glyburide