title: Progesterone inhibits chloride transport in human intestinal epithelial cells.
abstract: Several pieces of evidence suggest that female sex hormones may play a role in the regulation of electrolyte transport. We therefore hypothesized that female sex hormones might impair regulated transcellular chloride transport in human intestinal epithelial cells. The T84 cell line was used for electrophysiological studies. Changes in transepithelial resistance and short-circuit current (Isc) were measured via a dual voltage/current clamp in epithelial monolayers. Short-circuit current is equivalent to chloride secretion in T84 cells. Forskolin and 8-Br-cyclic adenosine monophosphate (cAMP) were used to activate cAMP-dependent Cl? transport. Ca2+-dependent secretion was stimulated by the receptor-mediated Ca2+ agonist carbachol. Acute exposure (30 minutes) to either progesterone or estradiol did not affect monolayer viability as reflected by transepithelial resistance. Moreover, the secretory response to both cAMP and Ca2+ agonists remained unaffected. In contrast, long-term exposure (24 hours) to physiological concentrations of progesterone (100 nM), but not estradiol, dose-dependently reduced the peak Isc induced by the cAMP-agonist forskolin from 125 +/- 2.7 mA. cm(2) in the control group to 96 +/- 2.5 mA. cm(2) in monolayers exposed to progesterone (n = 6 for each group; p <0.001). When the cAMP-analogue 8-Br-cAMP was used, the same behavior was observed (peak Isc = 112 +/- 1.6 mA. cm(2) vs 88 +/- 1.7 mA. cm(2) for control vs. progesterone-treated monolayers; n = 6 for each group; p <0.001). Taken together, our results suggest that progesterone but not estradiol inhibits cAMP-stimulated Cl- secretion in intestinal epithelial cells at a site distal to cyclic nucleotide generation.
authors.affiliation: Servicio de Cirugía I, 3a Norte, Hospital Clínico San Carlos, Universidad Complutense de Madrid, 28040 Madrid, Spain. jmayol@hcsc.insalud.es
authors.forename: Julio M
authors.initials: JM
authors.lastname: Mayol
authors.forename: Ana
authors.initials: A
authors.lastname: Arbeo-Escolar
authors.forename: Pilar
authors.initials: P
authors.lastname: Alarma-Estrany
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Adame-Navarrete
authors.forename: Jesús A
authors.initials: JA
authors.lastname: Fernández-Represa
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D002478:Cells, Cultured; D002712:Chlorides / Q000493:pharmacokinetics*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP; D004594:Electrophysiology; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects*; D011374:Progesterone / Q000494:pharmacology*
chemical_list: D002712:Chlorides; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011374:Progesterone; D004958:Estradiol; D000242:Cyclic AMP