Sex Differences in the Respiratory System Sex-specific effects of sex steroids on alveolar epithelial Na~+ transport

摘要

Haase M, Laube M, Thome UH. Sex-specific effects of sex steroids on alveolar epithelial Na+ transport. Am J Physiol Lung Cell Mol Physiol 312: L405-L414, 2017. First published January 6, 2017; doi:10.1152/ajplung.00275.2016.—Alveolar fluid clearance mediates perinatal lung transition to air breathing in newborn infants, which is accomplished by epithelial Na~+ channels (ENaC) and Na-K-ATPase. Male sex represents a major risk factor for developing respiratory distress, especially in preterm infants. We previously showed that male sex is associated with reduced epithelial Na~+ transport, possibly contributing to the sexual dimorphism in newborn respiratory distress. This study aimed to determine sex-specific effects of sex steroids on epithelial Na~+ transport. The effects of testosterone, 5alpha-dihydrotes-tosterone (DHT), estradiol, and progesterone on Na~+ transport and Na~+ channel expression were determined in fetal distal lung epithelial (FDLE) cells of male and female rat fetuses by Ussing chamber and mRNA expression analyses. DHT showed a minor effect only in male FDLE cells by decreasing epithelial Na~+ transport. However, flut-amide, an androgen receptor antagonist, did not abolish the gender imbalance, and testosterone lacked any effect on Na~+ transport in male and female FDLE cells. In contrast, estradiol and progesterone increased Na~+ transport and Na~+ channel expression especially in females, and prevented the inhibiting effect of DHT in males. Estrogen receptor inhibition decreased Na~+ channel expression and eliminated the sex differences. In conclusion, female sex steroids stimulate Na~+ transport especially in females and prevent the inhibitory effect of DHT in males. The ineffectiveness of testosterone suggests that Na~+ transport is largely unaffected by androgens. Thus, the higher responsiveness of female cells to female sex steroids explains the higher Na~+ transport activity, possibly leading to a functional advantage in females.