title: Estrogen induces neurite outgrowth via Rho family GTPases in neuroblastoma cells.
abstract: Estrogen (E2) has direct in vivo and in vitro effects, such as inducing neurite outgrowth, on neurons. We investigated the morphological changes and intracellular signaling pathway induced by E2 in neuroblastoma (SH-SY5Y) cells. The effect of medroxyprogesterone acetate (MPA) or progesterone (P4) on the E2-induced neurite outgrowth was also examined using SH-SY5Y cells. Neurite outgrowth was induced by E2 in association with the phosphorylation of Akt, and these effects of E2 were abolished by MPA but not by P4. Progesterone receptor antagonist RU486 blocked the inhibitory effects of MPA. Estrogen receptor antagonist ICI 182,780 and phosphatidylinositol 3-kinase inhibitor LY294002 inhibited the E2-induced neurite outgrowth. Because the Rho family of small GTPases has been shown to be involved in the regulation of neurite outgrowth, we examined the cross-talk among Rac1, Cdc42 and RhoA in the E2-induced neurite outgrowth. E2 immediately increased the Rac1 and Cdc42 activity and decreased the RhoA activity. E2-induced neurite outgrowth was attenuated in cells expressing dominant-negative mutants for Rac1 or Cdc42. These results suggest that regulation of Rho family GTPase activity by E2 is important for the neurite outgrowth in neuroblastoma cells, and that MPA may have an antagonistic effect against E2.
authors.affiliation: Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Japan. ktaka@med.id.yamagata-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Shunai
authors.initials: S
authors.lastname: Piao
authors.forename: Hizuru
authors.initials: H
authors.lastname: Yamatani
authors.forename: Botao
authors.initials: B
authors.lastname: Du
authors.forename: Limei
authors.initials: L
authors.lastname: Yin
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ohta
authors.forename: Jun
authors.initials: J
authors.lastname: Kawagoe
authors.forename: Keiko
authors.initials: K
authors.lastname: Takata
authors.forename: Seiji
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kurachi
mesh_terms: D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020741:rho GTP-Binding Proteins