Gender-Related Difference in Composition of Secretion from Esophageal Submucosal Mucous Glands, in Response to Stimulation of Serotonergic Pathway, in Patients with Gastroesophageal Reflux Disease

Abstract

Purpose: Protective potential of saliva and esophageal secretion in gastroesophageal reflux disease (GERD) patients is well established (Sarosiek J. et al., J P Gastroenterol 18: 20J–20Q, 1994). Stimulation of serotonin receptor 5HT-4 with tegaserod augments salivary and esophageal components of pre-epithelial defense in GERD (Majewski et al., CG&H, 5:430–8, 2007). The impact of gender on esophageal secretion in GERD patients during stimulation of 5HT-4 receptor remains to be addressed. Aim: To measure the rate of secretion of esophageal protective factors in females (F) and males (M) with chronic heartburn symptoms after 7 days of tegaserod (6 mg BID) or placebo administration. Methods: The study was conducted in 38 GERD patients (26 F & 12 M; mean age of 41) in a double-blind, placebo-controlled, cross-over design. Esophageal secretion was collected during the sophageal mucosal exposure to baseline NaCl, HCl/pepsin and final NaCl, using the esophageal perfusion catheter. Esophageal volume and its content of bicarbonates, non-bicarbonates, mucin, EGF, TGFα and PGE2 were measured using standard methodology. Results: In females after tegaserod, TGFα secretion during the esophageal mucosal exposure to HCl/pepsin solution increased from 15.0 ± 2.47 to 22.1 ± 2.71 pg/min (46.9%, P < 0.04). In contrast, in males, TGFα decreased by 51.5%, P < 0.03. The rate of esophageal EGF secretion in females during administration of tegaserod increased by 145% (P < 0.01) whereas in males increased by 50% (P > 0.10). The rate of esophageal PGE2 secretion during administration tegaserod increased by 81% (P= 0.076) in females only. Males responded by an evident increase of non-bicarbonates (by 69%) during administration of tegaserod, from 5.29 ± 0.56 to 8.95 ± 1.89 μEq/min (P= 0.08) and increase of bicarbonates by 143% but not females. Conclusion: 1. A significant enhancement of esophageal protective factors after tegaserod in both genders indicates that secretion of esophageal glands in GERD patients is mediated by serotonergic pathway. 2. The gender-related differences in the serotonergic secretory profiles suggest that 5HT-4 receptors in esophageal glands are influenced by sex hormones.