title: Oestradiol synthesized by female neurons generates sex differences in neuritogenesis.
abstract: Testosterone produced by the foetal testis is converted by male neurons to oestradiol, which masculinizes neuronal morphology. Female neurons are known to synthesize oestradiol in absence of exogenous testosterone. However, the role of neuronal oestradiol on the differentiation of foetal female neurons is unknown. Here we show that, due to endogenous neuronal oestradiol synthesis, female hippocampal neurons have higher expression of the neuritogenic protein Neurogenin 3 and enhanced neuritogenesis than males. Exogenous application of testosterone or its metabolite dihydrotestosterone increases Neurogenin 3 expression and promotes neuritogenesis in males, but reduces these parameters in females. Together our data indicate that gonadal-independent oestradiol synthesis by female neurons participates in the generation of sex differences in hippocampal neuronal development.
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avenida Doctor Arce 37, 28002 Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Ruiz-Palmero
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avenida Doctor Arce 37, 28002 Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ortiz-Rodriguez
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via G. Balzaretti 9, 20133 Milan, Italy.
authors.forename: Roberto Cosimo
authors.initials: RC
authors.lastname: Melcangi
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via G. Balzaretti 9, 20133 Milan, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Caruso
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avenida Doctor Arce 37, 28002 Madrid, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Garcia-Segura
authors.affiliation: Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: Rune
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avenida Doctor Arce 37, 28002 Madrid, Spain.
authors.forename: Maria-Angeles
authors.initials: MA
authors.lastname: Arevalo
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D012727:Sex Characteristics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004958:Estradiol; D009419:Nerve Tissue Proteins; C407737:Neurog3 protein, mouse