Female gender hormones regulate mRNA levels and function of the rat lung epithelial Na channel.

The epithelial Na channel (ENaC) plays a critical role in the active reabsorption of alveolar fluid at the time of birth or during pulmonary edema. Although rat (r) ENaC is regulated by glucocorticoids during fetal development, there are no data regarding the influence of gender hormones on ENaC expression or function. We report higher levels of mRNAs encoding the alpha-rENaC subunit or the cystic fibrosis transmembrane conductance regulator (CFTR) in the lungs of nonpregnant adult female relative to adult male Wistar rats. Combined, but not separate, administration of progesterone and 17 beta-estradiol increased mRNA levels encoding alpha-rENaC, gamma-rENaC, and CFTR within 24 h. We also found a dose-dependent increase in rENaC functional activity (as assessed by the amiloride-sensitive short-circuit current across primary monolayer cultures of alveolar epithelial cells mounted in Ussing chambers) after a 5-day incubation of cells in medium containing progesterone and 17 beta-estradiol. These findings suggest a gender-dependent influence on the lung's ability to recover from pulmonary edema and on the degree of airway fluid hydration in cystic fibrosis.