The present studies demonstrate that physiological actions of mineralocorticoid (aldosterone) on net intestinal Na+ absorption consists of two phases. The initial phase involves activation of PI3K that stimulates insertion of the α-subunit of Na+-K+-ATPase through a SGK-1-dependent pathway, increasing Na+-K+-ATPase activity and subsequent increased apical membrane NHE3 (aNHE3). The second phase involves SGK-1-dependent increases in total NHE3 and Na+-K+-ATPase (α-subunit) expression and activity although a contribution by aldosterone-mediated gene transcription of NHE3 cannot be ruled out. These actions reveal a complex, but orderly sequence of events that are essential for coordination of transport processes in both poles of epithelial cells and efficient net Na absorption.
