title: Oestradiol signalling through the Akt-mTORC1-S6K1.
abstract: The oestradiol plays an important role in normal brain development and exerts neuroprotective actions. Oestradiol is mainly produced in the ovary and in addition is locally synthesised in the brain. Most of the oestradiol functions have been associated with its capacity to directly bind and dimerize "classical oestrogen receptors" (ERs), alpha and beta. The ERs' actions have been classified as "genomic" and "non-genomic" depending on whether protein synthesis occurs through ER driven transcription or not. Indeed, recent evidence suggests that oestrogen may also act as a more general "trophic factor". Hence, we have studied the capacity of oestradiol to activate the PI3K/Akt pathway and its implication in axonal growth and neuronal morphogenesis. Our data show that when oestrogen receptors are blocked the axonal and dendritic lengths are reduced in mouse primary neurons. We found that Akt/Rheb/mTORC1 responds to ER activation in neurons and that some elements of this pathway are able to restore a normal neuronal morphology even in the presence of oestrogen receptor antagonist. All these data demonstrate a new mechanism regulated by oestradiol, at least in neuronal morphogenesis.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Univ. Autonoma de Madrid, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Varea
authors.forename: M
authors.initials: M
authors.lastname: Escoll
authors.forename: H
authors.initials: H
authors.lastname: Diez
authors.forename: J J
authors.initials: JJ
authors.lastname: Garrido
authors.forename: F
authors.initials: F
authors.lastname: Wandosell
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D002460:Cell Line; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D004958:Estradiol; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D058570:TOR Serine-Threonine Kinases; C512964:Rps6ka1 protein, mouse