title: Roles of 17ß-estradiol involve regulation of reelin expression and synaptogenesis in the dentate gyrus.
abstract: Studies on the role of 17β-estradiol (E2) in the hippocampus have mainly focused on CA1 and CA3 regions, whereas in dentate gyrus (DG), its role is largely unknown. Here, we examined potential functions of E2 in DG, particularly during development. Immunohistochemistry and in situ hybridization revealed abundance of estrogen receptor (ER)α, but not ERβ, expression in DG. Similar to CA1, analysis of synapse densities revealed a reduction in spine synapse number in DG molecular layer of immature rats and adult mice after inhibition of estradiol synthesis using letrozole. Interestingly, strong expression of ERα was found in Cajal-Retzius (CR) cells, which regulate neuronal migration and synaptogenesis via the extracellular matrix protein reelin. Immunoreactivity of aromatase, the final enzyme of estradiol synthesis, was strongest in mature granule cells. In hippocampal slice cultures, exogenous application of E2 caused an increase in reelin expression in CR cells, which was abolished after blockade of ERs using ICI182,780. Vice versa, inhibition of aromatase activity by letrozole resulted in reduced reelin expression, suggesting that E2 deriving from hippocampal sources contributes to the regulation of reelin as well as to the maintenance of spine synapses in DG. E2 further regulated Notch1, a signaling protein involved in neuronal differentiation.
authors.affiliation: University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Roland A
authors.initials: RA
authors.lastname: Bender
authors.forename: Lepu
authors.initials: L
authors.lastname: Zhou
authors.forename: Wiebke
authors.initials: W
authors.lastname: Wilkars
authors.forename: Lars
authors.initials: L
authors.lastname: Fester
authors.forename: Jan-Simon
authors.initials: JS
authors.lastname: Lanowski
authors.forename: Danny
authors.initials: D
authors.lastname: Paysen
authors.forename: Almut
authors.initials: A
authors.lastname: König
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: Rune
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis*; D018891:Dentate Gyrus / Q000254:growth & development / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D055495:Neurogenesis / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D013569:Synapses
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; D004958:Estradiol; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases