title: Control of aromatase in hippocampal neurons.
abstract: Our knowledge on estradiol-induced modulation of synaptic function in the hippocampus is widely based on results following the application of the steroid hormone to either cell cultures, or after the treatment of gonadectomized animals, thus ignoring local neuronal estrogen synthesis. We and others, however, have shown that hippocampus-derived estradiol also controls synaptic plasticity in the hippocampus. Estradiol synthesis in the hippocampus is regulated by several mechanisms, which are reviewed in this report. The regulation of the activity of aromatase, the final enzyme of estrogen biosynthesis, by Ca(2+) transients, is of particular interest. Aromatase becomes inactivated as soon as it is phosphorylated by Ca(2+)-dependent kinases upon calcium release from internal stores. Accordingly, thapsigargin dephosphorylates aromatase and stimulates estradiol synthesis by depletion of internal Ca(2+) stores. Vice versa, letrozole, an aromatase inhibitor, phosphorylates aromatase and reduces estradiol synthesis. Treatment of the cultures with 17β-estradiol results in phosphorylation of the enzyme and increased aromatase protein expression, which suggests that estradiol synthesis in hippocampal neurons is regulated in an autocrine manner.
authors.affiliation: University Medical Center Hamburg Eppendorf, Institute of Neuroanatomy, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Fester
authors.affiliation: University Medical Center Hamburg Eppendorf, Institute of Neuroanatomy, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Brandt
authors.affiliation: Department of Biochemistry and Signal Transduction, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Windhorst
authors.affiliation: University Medical Center Hamburg Eppendorf, Institute of Neuroanatomy, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Pröls
authors.affiliation: University Medical Center Hamburg Eppendorf, Institute of Neuroanatomy, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Bläute
authors.affiliation: University Medical Center Hamburg Eppendorf, Institute of Neuroanatomy, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: rune@uke.de.
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: Rune
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: D004958:Estradiol; D001141:Aromatase; D002118:Calcium
keywords: 17β-Estradiol; Aromatase; Aromatase immunohistochemistry; Aromatase phosphorylation; Ca(2)(+) transients; Neurons