Estrogen-regulated synaptogenesis in the hippocampus: Sexual dimorphism in vivo but not in vitro

Lars Fester, Janine Prange-Kiel, Lepu Zhou, Breda V. Blittersdorf, Julia Böhm, Hubertus Jarry, Michael Schumacher, Gabriele M. Rune

Research output: Contribution to journalReview articlepeer-review

64 Scopus citations

Abstract

Hippocampal neurons are capable of synthesizing estradiol de novo. Estradiol synthesis can be suppressed by aromatase inhibitors and by knock-down of steroid acute regulatory protein (StAR), whereas elevated levels of substrates of steroidogenesis enhance estradiol synthesis. In rat hippocampal cultures, the expression of estrogen receptors (ERs) and synaptic proteins, as well as synapse density, correlated positively with aromatase activity, regardless of whether the cultures originated from males or females. All effects induced by the inhibition of aromatase activity were rescued by application of estradiol to the cultures. In vivo, however, systemic application of letrozole, an aromatase inhibitor, induced synapse loss in female rats, but not in males. Furthermore, in the female hippocampus, density of spines and spine synapses varied with the estrus cycle. In addressing this in vivo-in vitro discrepancy, we found that gonadotropin-releasing hormone (GnRH) regulated estradiol synthesis via an aromatase-mediated mechanism and consistently regulated spine synapse density and the expression of synaptic proteins. Along these lines, GnRH receptor density was higher in the hippocampus than in the cortex and hypothalamus, and estrus cyclicity of spinogenesis was found in the hippocampus, but not in the cortex. Since GnRH receptor expression also varies with the estrus cycle, the sexual dimorphism in estrogen-regulated spine synapse density in the hippocampus very likely results from differences in the GnRH responsiveness of the male and the female hippocampus. This article is part of a Special Issue entitled 'Neurosteroids'.

Original languageEnglish (US)
Pages (from-to)24-29
Number of pages6
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume131
Issue number1-2
DOIs
StatePublished - Aug 1 2012

Keywords

  • Aromatase
  • GnRH
  • Hippocampus
  • Letrozole
  • Spine synapses

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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