The interaction of glucocorticoids and progesterone distinctively affects epithelial sodium transport.

ABSTRACT

PURPOSE: Glucocorticoids and progesterone exert stimulatory effects on epithelial Na(+) transport, including increased mRNA expression of the participating ion transporters (epithelial Na(+) channels [ENaC] and Na,K-ATPases) and their electrophysiological activity. Fetuses threatened by preterm labor may receive high doses of glucocorticoids to stimulate lung maturation and are naturally exposed to high levels of female sex steroids. However, it is still unknown how the combination of both hormones influences the epithelial Na(+) transport, which is crucial for alveolar fluid clearance. METHODS: Fetal distal lung epithelial cells were incubated in media supplemented with dexamethasone and progesterone. Real-time qPCR and Ussing chamber analysis were used to determine the effects on ENaC mRNA expression and channel activity. In addition, the specific progesterone receptor antagonist (PF-02367982) and the glucocorticoid receptor antagonist mifepristone were used to identify the involved hormone receptors. RESULTS: Both dexamethasone and progesterone increased ENaC subunit expression and channel activity. However, the combination of dexamethasone and progesterone reduced the α- and γ-ENaC subunit expression compared to the effect of dexamethasone alone. Furthermore, higher dexamethasone concentrations in combination with progesterone also significantly reduced Na(+) transport in Ussing chamber measurements. Hormone receptor antagonists showed that inhibition of the progesterone receptor increased the mRNA expression of α- and γ-ENaC, whereas mifepristone decreased mRNA expression of all ENaC subunits. CONCLUSION: Glucocorticoids and progesterone individually increase ENaC mRNA expression; however, the combination of both hormones decreases the stimulatory effects of dexamethasone on Na(+) transport and ENaC mRNA expression.