Sex-specific effects of sex steroids on alveolar epithelial Na+ transport
M Haase, M Laube, UH Thome - American Journal of …, 2017 - journals.physiology.org
M Haase, M Laube, UH Thome
American Journal of Physiology-Lung Cellular and Molecular …, 2017•journals.physiology.orgAlveolar 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 …
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 …
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, 5α-dihydrotestosterone (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, flutamide, 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.
American Physiological Society
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