Gonadotropin-releasing hormone regulates spine density via its regulatory role in hippocampal estrogen synthesis

Janine Prange-Kiel, Hubertus Jarry, Michael Schoen, Patrick Kohlmann, Christina Lohse, Lepu Zhou, Gabriele M. Rune

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


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 expres sion 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 five fold 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.

Original languageEnglish (US)
Pages (from-to)417-426
Number of pages10
JournalJournal of Cell Biology
Issue number2
StatePublished - Jan 28 2008

ASJC Scopus subject areas

  • Cell Biology


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