Interaction of estrogen and progesterone in the regulation of sodium channels in collecting tubular cells

Background: Renal Na⁺ handling differs between males and females. Further, within females Na⁺ metabolism changes during the menstrual cycle and pregnancy. Estrogen and progesterone could regulate α, β and γ amiloride-sensitive epithelial sodium channel (ENaC) subunit mRNA levels in female rat kidney. The aim of our study is to clarify the role of the female gender steroids in the regulation of ENaC activity. Methods: We conducted an in vitro study on cultured collecting tubular cells. The collecting tubular cells were cultured under different concentrations of estrogen and/or progesterone. We analyzed the mRNA expression and protein translation of ENaC by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Sodium channel activity was measured by short circuit current. Results: Estrogen and/or progesterone alone mildly increased ENaC activity. A low concentration of estrogen together with progesterone stimulated ENaC activity more than 2-fold. A high concentration of estrogen almost completely inhibited the stimulated ENaC activity. Conclusion: Female gender steroid hormones affect RNA expression, protein translation and ENaC activity in renal collecting tubule cells. The effects might suggest that pre-menstruation edema is a result of subtle interaction between the female gender steroid hormones on ENaC in renal collecting tubule cells.