Modulation of synaptic plasticity in the hippocampus by hippocampus-derived estrogen and androgen
Abstract
The hippocampus synthesizes estrogen and androgen in addition to the circulating sex steroids. Synaptic modulation by hippocampus-derived estrogen or androgen is essential to maintain healthy memory processes. Rapid actions (1-2h) of 17β-estradiol (17β-E2) occur via synapse-localized receptors (ERα or ERβ), while slow genomic E2 actions (6-48h) occur via classical nuclear receptors (ERα or ERβ). The long-term potentiation (LTP), induced by strong tetanus or theta-burst stimulation, is not further enhanced by E2 perfusion in adult rats. Interestingly, E2 perfusion can rescue corticosterone (stress hormone)-induced suppression of LTP. The long-term depression is modulated rapidly by E2 perfusion. Elevation of the E2 concentration changes rapidly the density and head structure of spines in neurons. ERα, but not ERβ, drives this enhancement of spinogenesis. Kinase networks are involved downstream of ERα. Testosterone (T) or dihydrotestosterone (DHT) also rapidly modulates spinogenesis. Newly developed Spiso-3D mathematical analysis is used to distinguish these complex effects by sex steroids and kinases. It has been doubted that the level of hippocampus-derived estrogen and androgen may not be high enough to modulate synaptic plasticity. Determination of the accurate concentration of E2, T or DHT in the hippocampus is enabled by mass-spectrometric analysis in combination with new steroid-derivatization methods. The E2 level in the hippocampus is approximately 8nM for the male and…
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The hippocampal strata CA1 Rad, CA1 LMol, and PoDG are well-established sexually dimorphic regions in which microglia display sex-specific differences in various properties.
“We focused our investigation on different hippocampal strata: cornu ammonis (CA)1 stratum radiatum (Rad) and CA1 stratum lacunosum-moleculare (LMol), as well as the dentate gyrus polymorphic layer (PoDG), which are some of the well-established sexually dimorphic regions, in which microglia display sex-specific differences in various properties [51–53].”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [53]
The hippocampus is rich in estradiol receptors where neurons locally synthesize estrogen and testosterone during adulthood, particularly pyramidal neurons of CA1 and granule cells of DG.
“This area is also rich in estradiol receptors where neurons locally synthesize estrogen and testosterone during adulthood, particularly the pyramidal neurons of the CA1 and the granule cells of the DG [51–53].”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [53]
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Sex differences in hippocampal function
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Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders
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“This area is also rich in estradiol receptors where neurons locally synthesize estrogen and testosterone during adulthood, particularly the pyramidal neurons of the CA1 and the granule cells of the DG [51–53].”
- Authors
- Ooishi, Y., Kawato, S., Hojo, Y., Hatanaka, Y., Higo, S., Murakami, G., Komatsuzaki, Y., Ogiue-Ikeda, M., Kimoto, T., & Mukai, H.
- Affiliations
- The University of Tokyo (JP)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Kawato, Suguru
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 131
- Issue
- 1-2
- Pages
- 37-51
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W2019747892
- Cited by
- 133
- References
- 4
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 6 · 2023: 4 · 2022: 4 · 2021: 8 · 2020: 8 · 2019: 15 · 2018: 12 · 2017: 11 · 2016: 13 · 2015: 16 · 2014: 11 · 2013: 10 · 2012: 4
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (23657098, 23700369, 22570155, 23700496, 21370064)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- hippocampus, estradiol, testosterone, dihydrotestosterone, synaptic plasticity, long-term potentiation, long-term depression, spinogenesis, dendritic spine morphology, estrogen receptor alpha, estrogen receptor beta, corticosterone, kinase signaling, sex steroids, memory
- MeSH terms
- Animals, Estradiol, Female, Hippocampus, Male, Memory, Neuronal Plasticity, Dihydrotestosterone, Testosterone, Long-Term Potentiation, Long-Term Synaptic Depression, Estrogen Receptor alpha, Estrogen Receptor beta, Dendritic Spines, Rats
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