17β-Estradiol and 17α-estradiol induce rapid changes in cytoskeletal organization in cultured oligodendrocytes

Dramatic changes in the cytoskeleton and the morphology of oligodendrocytes (OLs) occur during various stages of the myelination process. OLs in culture produce large membrane sheets containing cytoskeletal veins of microtubules and actin filaments. We recently showed that estrogen receptors (ER) related to ERα/β were expressed in the membrane sheets of mature OLs in culture. Ligation of these or other membrane ERs in OLs with both 17β- and 17α-estradiol mediated rapid non-genomic signaling. Here, we show that estrogens also mediate rapid non-genomic remodeling of the cytoskeleton in mature OLs in culture. 17β-Estradiol caused a rapid loss of microtubules and the actin cytoskeleton in the OL membrane sheets. It also increased phosphorylation of the actin filament-severing protein cofilin, thus inactivating it. Staining for actin barbed ends with rhodamine-actin showed that it decreased the amount of actin barbed ends. 17α-Estradiol, on the other hand, increased the percentage of cells with abundant staining of actin filaments and actin barbed ends, suggesting that it stabilized and/or increased the dynamics of the actin cytoskeleton. The specific ERα and ERβ agonists, 4,4',4″-(4-propyl-(1H)-pyrazole-1,3,5-triyl) trisphenol (PPT) and diarylpropionitrile 2,3-bis(4-hydroxy-phenyl)-propionitrile (DPN), respectively, also caused the rapid phosphorylation of cofilin. Estrogen-induced phosphorylation of cofilin was inhibited by Y-27632, a specific inhibitor of the Rho-associated protein serine/threonine kinase (ROCK). The Rho/ROCK/cofilin pathway is therefore implicated in actin rearrangement via estrogen ligation of membrane ERs, which may include forms of ERα and ERβ. These results indicate a role for estrogens in modulation of the cytoskeleton in mature OLs, and thus in various processes required for myelinogenesis.