title: Oestrogen synthesis in the hippocampus: role in axon outgrowth.
abstract: Ovarian oestrogens have been postulated to be neuroprotective. It has also been shown that considerable amounts of oestrogens are synthesised in hippocampal neurones. In the present study, we focused on a potential role of hippocampus-derived oestradiol compared to gonad-derived oestradiol on axon outgrowth of hippocampal neurones. To address the role of hippocampus-derived oestradiol, we inhibited oestrogen synthesis by treatment of neonatal hippocampal cell cultures with letrozole, a specific aromatase inhibitor. As an alternative, we used siRNA against steroidogenic acute regulatory protein (StAR). Axon outgrowth and GAP-43 expression were significantly down-regulated in response to letrozole and in siRNA-StAR transfected cells. The effects after inhibition of oestrogen synthesis in response to letrozole and in siRNA-StAR transfected cells were reversed by oestrogen supplementation. No difference was found between ovariectomised animals, cycling animals at pro-oestrus and ovariectomised and subsequently oestradiol-treated animals. However, high pharmacological doses of oestradiol promoted axon outgrowth, which was possible to abolish by the oestrogen receptor antagonist ICI 182,780. Our results show that oestradiol-induced neurite outgrowth is very likely mediated by genomic oestrogen receptors and requires higher doses of oestradiol than physiological serum concentrations derived from the gonads.
authors.affiliation: Institute of Anatomy I, Cellular Neurobiology, University Medical Center, Hamburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: von Schassen
authors.forename: L
authors.initials: L
authors.lastname: Fester
authors.forename: J
authors.initials: J
authors.lastname: Prange-Kiel
authors.forename: C
authors.initials: C
authors.lastname: Lohse
authors.forename: C
authors.initials: C
authors.lastname: Huber
authors.forename: M
authors.initials: M
authors.lastname: Böttner
authors.forename: G M
authors.initials: GM
authors.lastname: Rune
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000494:pharmacology; D002478:Cells, Cultured; D015536:Down-Regulation; D004958:Estradiol / Q000096:biosynthesis* / Q000097:blood; D019922:GAP-43 Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D000077289:Letrozole; D016501:Neurites / Q000187:drug effects / Q000201:enzymology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D014018:Tissue Distribution; D014230:Triazoles / Q000494:pharmacology; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D047072:Aromatase Inhibitors; D019922:GAP-43 Protein; D009570:Nitriles; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D014230:Triazoles; D000098682:Steroidogenic Acute Regulatory Protein; D004958:Estradiol; D000077289:Letrozole; D001141:Aromatase