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Cited by 86Neuroscience and Neuropharmacology ResearchEstrogen and related hormone effectsMemory and Neural Mechanisms

Hippocampal Synthesis of Sex Steroids and Corticosteroids: Essential for Modulation of Synaptic Plasticity

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Hojo, Yasushi, Higo, Shimpei, Kawato, Suguru, Hatanaka, Yusuke, Ooishi, Yuuki, Murakami, Gen, Ishii, Hirotaka, Komatsuzaki, Yoshimasa +3 more·2011·Frontiers in Endocrinology
DOI 10.3389/fendo.2011.00043PMC PMC3356120
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Abstract

Sex steroids play essential roles in the modulation of synaptic plasticity and neuroprotection in the hippocampus. Accumulating evidence shows that hippocampal neurons synthesize both estrogen and androgen. Recently, we also revealed the hippocampal synthesis of corticosteroids. The accurate concentrations of these hippocampus-synthesized steroids are determined by liquid chromatography-tandem mass-spectrometry in combination with novel derivatization. The hippocampal levels of 17β-estradiol (E2), testosterone (T), dihydrotestosterone (DHT), and corticosterone (CORT), are 5-15 nM, and these levels are sufficient to modulate synaptic plasticity. Hippocampal E2 modulates memory-related synaptic plasticity not only slowly/genomically but also rapidly/non-genomically. Slow actions of E2 occur via classical nuclear receptors (ERα or ERβ), while rapid E2 actions occur via synapse-localized or extranuclear ERα or ERβ. Nanomolar concentrations of E2 change rapidly the density and morphology of spines in hippocampal neurons. ERα, but not ERβ, drives this enhancement/suppression of spinogenesis in adult animals. Nanomolar concentrations of androgens (T and DHT) and CORT also increase the spine density. Kinase networks are involved downstream of ERα and androgen receptor. Newly developed Spiso-3D mathematical analysis is useful to distinguish these complex effects by sex steroids and kinases. Significant advance has been achieved in investigations of rapid modulation by E2 of the long-term depression or the long-term potentiation.

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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 [51]

    The “Synaptic or extranuclear estrogen receptors” section describes sex differences in hippocampal neurons and estradiol levels. It does not establish CA1 Rad, CA1 LMol, and PoDG as sexually dimorphic strata or report sex-specific differences in their microglia; the cited passages have no page numbers. (LLM, conf=0.76)

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  • 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 [51]

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Research works printed but not linked: 2

  1. Yamashita K. Okuyama M. Watanabe Y. Honma S. Kobayashi S. Numazawa M. (2007b). Highly sensitive determination of estrone and estradiol in human serum by liquid chromatography-electrospray ionization tandem mass spectrometry. Steroids 72, 819– 827 10.1016/j.steroids.2007.07.003 17716700 · DOI
  2. Yang S. N. Tang Y. G. Zucker R. S. (1999). Selective induction of LTP and LTD by postsynaptic [Ca2+]i elevation. J. Neurophysiol. 81, 781– 787 10036277

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Authors
Hojo, Y., Higo, S., Kawato, S., Hatanaka, Y., Ooishi, Y., Murakami, G., Ishii, H., Komatsuzaki, Y., Ogiue-Ikeda, M., Mukai, H., & Kimoto, T.
Affiliations
  • Japan Science and Technology Agency (JP)
  • The University of Tokyo (JP)
  • Nihon University (JP)
Corresponding author
Kawato, Suguru
ORCID
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2011
Volume
2
Pages
43-43
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2011.00043
PMC
PMC3356120
OpenAlex
W2138331726
Cited by
86
References
109
Citations by year
2026: 1 · 2025: 3 · 2024: 8 · 2023: 3 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 9 · 2017: 6 · 2016: 7 · 2015: 7 · 2014: 13 · 2013: 3 · 2012: 2
FWCI
2.39
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Japan Society for the Promotion of Science (23657098, 23700369, 22570155, 22790229, 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, sex steroids, corticosteroids, estrogen, androgens, estradiol, testosterone, dihydrotestosterone, corticosterone, synaptic plasticity, dendritic spines, spinogenesis, androgen receptor, estrogen receptor alpha, estrogen receptor beta, kinase signaling, long-term potentiation, long-term depression, memory, neuroprotection, steroid synthesis

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