Estrogen synthesis in the brain—Role in synaptic plasticity and memory
Abstract
Estrogen and androgen are synthesized from cholesterol locally in hippocampal neurons of adult animals. These neurosteroids are synthesized by cytochrome P450s and hydroxysteroid dehydrogenases (HSDs) and 5alpha-reductase. The expression levels of enzymes are as low as 1/200-1/50,000 of those in endocrine organs, however these numbers are high enough for local synthesis. Localization of P450(17alpha), P450arom, 17beta-HSD and 5alpha-reductase is observed in principal glutamatergic neurons in CA1, CA3 and the dendate gyrus. Several nanomolar levels of estrogen and androgen are observed in the hippocampus. Estrogen modulates memory-related synaptic plasticity not only slowly but also rapidly in the hippocampus. Rapid action of 17beta-estradiol via membrane receptors is demonstrated for spinogenesis and long-term depression (LTD). The enhancement of LTD by 1-10nM estradiol occurs within 1 h. The density of spine is increased in CA1 pyramidal neurons within 2h after application of estradiol. The density of spine-like structure is, however, decreased by estradiol in CA3 pyramidal neurons. ERalpha, but not ERbeta, induces the same enhancement/suppression effects on both spinogenesis and LTD.
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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 [52]
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 [52]
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- Authors
- Hojo, Y., Murakami, G., Mukai, H., Higo, S., Hatanaka, Y., Ogiue-Ikeda, M., Ishii, H., Kimoto, T., & Kawato, S.
- Affiliations
- Japan Science and Technology Agency (JP)
- Corresponding author
- Kawato, Suguru
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 290
- Issue
- 1-2
- Pages
- 31-43
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2090604814
- Cited by
- 214
- References
- 6
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 10 · 2023: 10 · 2022: 8 · 2021: 7 · 2020: 11 · 2019: 4 · 2018: 8 · 2017: 7 · 2016: 15 · 2015: 17 · 2014: 11 · 2013: 23 · 2012: 16
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- 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
- estrogen synthesis, hippocampus, synaptic plasticity, memory, neurosteroids, cytochrome P450 aromatase, 17β-hydroxysteroid dehydrogenase, 5α-reductase, estradiol, membrane estrogen receptor, estrogen receptor alpha, estrogen receptor beta, long-term depression, spinogenesis, dendritic spines, CA1 pyramidal neurons, CA3 pyramidal cells, glutamatergic neurons, androgen production
- MeSH terms
- Animals, Brain, Estrogens, Humans, Memory, Neuronal Plasticity, Synapses
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