Permalink : http://hdl.handle.net/2115/90488

Many types of cells in the monocyte‒macrophage linage have been shown to be regulated by estrogen. In addition, a body of information suggests that the Na, K-ATPase pump could be a target of 17β-estradiol (E2) in various types of cells. In this study, we explored the effects of E2 on the Na, K-ATPase in macrophage-like RAW 264.7 cells. E2 treatment of RAW 264.7 cells led to biphasic stimulation of Na, K-ATPase activity: an early activation via the cell surface receptor GPR30 and a late upregulation by nuclear estrogen receptor (ER)-activated signals. Antagonization of GPR30 by G15 abolished E2-induced early activation of Na, K-ATPase, while inhibition of ER signals nullified its late upregulation of Na, K-ATPase activity in a dose-dependent manner. Furthermore, short-term treatment with E2 induced phosphorylation of the Na, K-ATPase α1- subunit at Tyr-10, which relied on was related to an increase i n the N a＋ affinity of Na, K-ATPase. These results illustrate the involvement of two diffe rent signaling pathways in the regulation of Na, K-ATPase by E2.