title: Gonadotropin-releasing hormone regulates spine density via its regulatory role in hippocampal estrogen synthesis.
abstract: Spine density in the hippocampus changes during the estrus cycle and is dependent on the activity of local aromatase, the final enzyme in estrogen synthesis. In view of the abundant gonadotropin-releasing hormone receptor (GnRH-R) messenger RNA expression in the hippocampus and the direct effect of GnRH on estradiol (E2) synthesis in gonadal cells, we asked whether GnRH serves as a regulator of hippocampal E2 synthesis. In hippocampal cultures, E2 synthesis, spine synapse density, and immunoreactivity of spinophilin, a reliable spine marker, are consistently up-regulated in a dose-dependent manner at low doses of GnRH but decrease at higher doses. GnRH is ineffective in the presence of GnRH antagonists or aromatase inhibitors. Conversely, GnRH-R expression increases after inhibition of hippocampal aromatase. As we found estrus cyclicity of spine density in the hippocampus but not in the neocortex and GnRH-R expression to be fivefold higher in the hippocampus compared with the neocortex, our data strongly suggest that estrus cycle-dependent synaptogenesis in the female hippocampus results from cyclic release of GnRH.
authors.affiliation: Institute of Anatomy I: Cellular Neurobiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. prange-kiel@uke.uni-hamburg.de
authors.forename: Janine
authors.initials: J
authors.lastname: Prange-Kiel
authors.forename: Hubertus
authors.initials: H
authors.lastname: Jarry
authors.forename: Michael
authors.initials: M
authors.lastname: Schoen
authors.forename: Patrick
authors.initials: P
authors.lastname: Kohlmann
authors.forename: Christina
authors.initials: C
authors.lastname: Lohse
authors.forename: Lepu
authors.initials: L
authors.lastname: Zhou
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: Rune
mesh_terms: D000818:Animals; D004958:Estradiol / Q000096:biosynthesis*; D004971:Estrus; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D000099273:Neurabins
chemical_list: D004958:Estradiol; D007987:Gonadotropin-Releasing Hormone; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000099273:Neurabins