492 Female Sex Steroids Modulate Alveolar Epithelial Sodium Transport

Background and aims: Sodium transport plays a crucial role in alveolar fluid clearance (AFC), where sodium enters the alveolar epithelial cells through apical sodium channels (ENaC) and is extruded by basolateral Na, K-ATPases. Women with acute respiratory distress syndrome have higher AFC and higher survival than males. Female sex steroids are supposedly responsible for these genderrelated differences. Therefore, the aim of this study was to analyze the effects of estrogen (E2) and progesterone (P) on epithelial sodium transport. Methods: Isolated alveolar epithelial cells from 18-19-day gestational age rat fetuses, grown in serum-free media supplemented with E2 and P were studied, involving Real-Time PCR analysis, single-channel patch clamp, Ussing chamber measurements and Western blotting. Results: rtPCR revealed an increase of α- and β-ENaC in media supplemented with E2 and P, where the effect on α-ENaC was most pronounced in P-rich media. The mRNA-level of γ-ENaC was not altered, but the Na-K-ATPase-β 1 subunit and the CFTR-mRNA expression were increased by E2 and P supplementation. Single-channel patch clamp analysis showed highly-selective and non-selective ENaC in the examined cells. The percentage of responsive patches increased from 45% in nonsupplemented media to 91% in the presence of E2 and P. Short-circuit current ( I SC ) measurement showed that the baseline, amiloride- and ouabainsensitive I SC were elevated by E2 and P in a dosedependent manner. Conclusions: These results demonstrate increased expression of epithelial transport proteins by female sex steroids. Furthermore, vectorial sodium transport was increased. The findings may explain the observed survival advantage.