Gender Difference in Duodenal HCO3-Response to Mucosal Acidification: Importance of Up-Regulation of ASIC3 by Estradiol

In the present study, we investigated the mechanism responsible for the gender difference in the acid‐induced duodenal HCO3‐ secretion. Male and female SD rats were used after 18 h fasting. Under urethane anesthesia, a proximal duodenal loop was perfused with saline, and HCO3‐ secretion was measured. Mmucosal acidification was performed by exposing the loop to 10 mM HCl for 10 min. Ovariectomy was performed 2 weeks before the experiments, and 17β‐estradiol was given i.m. on day 3, 7 and 10 after the operation. Although no difference was found in the HCO3‐ responses to PGE2 and capsaicin between male and female rats, the response to acid was significantly greater in female rats. However, this different response to acid was dissipated by ovariectomy, and this effect was antagonized by the repeated estradiol treatment. The expression of ASIC3 mRNA was greater in female rats and down‐regulated by ovariectomy, in an estradiol‐dependent manner. These results suggest that the acid induced‐HCO3‐ secretion was greater in female than male rats, and the mechanism for the different response may be accounted for by the up‐regulation of ASIC3 expression in female rats.