Abstract
There is general acceptance that the estrogen receptor can act as a transcription factor. However, estrogens can also bind to receptors that are located at the plasma membrane and stimulate rapid intracellular signaling processes. We recently showed that a membrane‐associated estrogen receptor (mER) is present within myelin and at the oligodendrocyte (OL) plasma membrane. To understand the physiological function of mER in OLs, we investigated its cellular localization and involvement in rapid signaling in CG4 cells and OL primary cultures. An ERα was expressed along the lacy network of veins in the membrane sheets and in the perikaryon and nucleus in OLs. ERβ was located in the nucleus, and to a lesser extent along the veins. The expression of ERα and ERβ in OL membranes was confirmed by Western analysis of isolated membranes. OL membranes mainly had truncated forms of ERα, 53 and 50 kDa, in addition to some 65 kDa form, whereas ERβ was a 54 kDa form. CG4 cells and OLs were pulsed with 17α‐ and 17β‐estradiol for various times and the total lysates were analyzed for phosphorylated kinases. Both 17α‐ and 17β‐estradiol elicited rapid phosphorylation of p42/44MAPK, Akt, and GSK‐3β within 8 min. This rapid signaling is consistent with estradiol ligation of a membrane form of ER. Since 17α‐estradiol is produced at higher concentrations than 17β‐estradiol in the brain of both sexes, signaling via 17α‐estradiol‐liganded mER may have an important function in OLs. © 2008 Wiley‐Liss, Inc.