Gender Differences in Serotonin Signaling in Patients with Diarrhea-predominant Irritable Bowel Syndrome.
Atslēgvārdi
Abstrakts
Objective Gender differences, including differences in the prevalence, subtypes and the effectiveness of treatment, are generally recognized in irritable bowel syndrome (IBS). Although serotonin type 3 receptor (5-HT3R) antagonists appear to be more effective in women with diarrhea predominant IBS (IBS-D) than they are in men, the mechanisms underlying these effects remain unclear. The aim of the present was to investigate the gender differences in 5-HT signaling. Methods The subjects were selected from outpatients with IBS-D and healthy controls. Their rectal mucosal S100A, tryptophan hydroxylase (TPH) and 5-HT transporter (5-HTT, SERT, SLC6A4) mRNA expression levels were measured. Clinical symptoms were evaluated using the gastrointestinal symptom rating scale (GSRS) and the self-rating depression scale (SDS). Results The study population of 100 subjects included 47 IBS-D patients and 53 age- and gender-matched healthy controls. The S100A9 (5.20 vs. 1.90, p=0.001) and SLC6A4 (2.00 vs. 1.00, p=0.019) mRNA levels in the rectal mucosa of women with IBS-D were significantly higher than those in men. Among the healthy controls, the S100A10 expression levels in men were higher than those in women (1.33 vs. 0.82, p=0.005). The S100A8 and S100A10 expression levels in women with IBS-D were positively correlated with their diarrhea scores (r=0.55 and 0.58, p<0.05). Conclusion 5-HT signaling might be a major contributor to the symptoms of IBS in men, and the differences may be associated with the effectiveness of 5-HT3R antagonists.