title: G protein-coupled estrogen receptor is required for the neuritogenic mechanism of 17β-estradiol in developing hippocampal neurons.
abstract: Estradiol promotes neuritogenesis in developing hippocampal neurons by a mechanism involving the upregulation of neurogenin 3, a Notch-regulated transcription factor. In this study we have explored whether G-protein coupled estrogen receptor 1 (GPER) participates in this hormonal action. GPER agonists (17β-estradiol, G1, ICI 182,780) increased neurogenin 3 expression and neuritogenesis in mouse primary hippocampal neurons and this effect was blocked by the GPER antagonist G15 and by a siRNA for GPER. In addition, GPER agonists increased Akt phosphorylation in ser473, which is indicative of the activation of phosphoinositide-3-kinase (PI3K). G15 or GPER silencing prevented the estrogenic induction of Akt phosphorylation. Furthermore, the PI3K inhibitor wortmannin prevented the effect of G1 and estradiol on neurogenin 3 expression and the effect of estradiol on neuritogenesis. These findings suggest that GPER participates in the control of hippocampal neuritogenesis by a mechanism involving the activation of PI3K signaling.
authors.affiliation: Instituto Cajal, CSIC, E-28002 Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Ruiz-Palmero
authors.forename: Maria
authors.initials: M
authors.lastname: Hernando
authors.forename: Luis M
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: Maria-Angeles
authors.initials: MA
authors.lastname: Arevalo
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D015870:Gene Expression; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D061251:Primary Cell Culture; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011960:Receptors, Estrogen / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D051792:Basic Helix-Loop-Helix Proteins; D004958:Estradiol; D004967:Estrogens; D000077267:Fulvestrant; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D000077191:Wortmannin; C532507:GPER1 protein, mouse; C407737:Neurog3 protein, mouse