title: Synaptopodin is regulated by aromatase activity.
abstract: Locally synthesized estradiol plays an important role in synaptic plasticity in the hippocampus. We have previously shown that in hippocampal neurons, activity of the enzyme aromatase, which converts testosterone into estradiol, is reduced via Ca2+-dependent phosphorylation. Synaptopodin is a highly estrogen responsive protein, and it has been shown that it is an important regulator of synaptic plasticity, mediated by its close association with internal calcium stores. In this study, we show that the expression of synaptopodin is stronger in the hippocampus of female animals than in that of male animals. Phosphorylation of aromatase, using letrozole, however, down-regulates synaptopodin immunohistochemistry in the hippocampus of both male and females. Similarly, in aromatase knock-out mice synaptopodin expression in the hippocampus is reduced sex independently. Using primary-dissociated hippocampal neurons, we found that evoked release of Ca2+from internal stores down-regulates aromatase activity, which is paralleled by reduced expression of synaptopodin. Opposite effects were achieved after inhibition of the release. Calcium-dependent regulation of synaptopodin expression was abolished when the control of aromatase activity by the Ca2+transients was disrupted. Our data suggest that the regulation of aromatase activity by Ca2+transients in neurons contributes to synaptic plasticity in the hippocampus of male and female animals as an on-site regulatory mechanism.
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Hamburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Fester
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Hamburg, Germany.
authors.forename: Lepu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Hamburg, Germany.
authors.forename: Christiana
authors.initials: C
authors.lastname: Ossig
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Hamburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Labitzke
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Hamburg, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Bläute
authors.affiliation: Department of Biology, Technische Universität Dresden, Dresden, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Bader
authors.affiliation: Department of Biology, Technische Universität Dresden, Dresden, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Vollmer
authors.affiliation: Department of Experimental Endocrinology, University of Goettingen, Goettingen, Germany.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Jarry
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Hamburg, Germany.
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: Rune
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D000077289:Letrozole; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D008840:Microfilament Proteins; D009570:Nitriles; C503969:Synpo protein, rat; D014230:Triazoles; D000077289:Letrozole; D001141:Aromatase
keywords: aromatase; calcium transients; spine apparatus; spine synapses; synaptopodin