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Updated: Apr 21, 2026

Ovariectomy and 17β-estradiol Replacement in Rats and Mice: A Visual Demonstration
Published on: June 7, 2012
17β-estradiol modulates gene expression in the female mouse cerebral cortex
Gwendolyn I Humphreys1, Yvonne S Ziegler1, Ann M Nardulli1
1Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
Abstract:
17β-estradiol (E2) plays critical roles in a number of target tissues including the mammary gland, reproductive tract, bone, and brain. Although it is clear that E2 reduces inflammation and ischemia-induced damage in the cerebral cortex, the molecular mechanisms mediating the effects of E2 in this brain region are lacking. Thus, we examined the cortical transcriptome using a mouse model system. Female adult mice were ovariectomized and implanted with silastic tubing containing oil or E2. After 7 days, the cerebral cortices were dissected and RNA was isolated and analyzed using RNA-sequencing. Analysis of the transcriptomes of control and E2-treated animals revealed that E2 treatment significantly altered the transcript levels of 88 genes. These genes were associated with long term synaptic potentiation, myelination, phosphoprotein phosphatase activity, mitogen activated protein kinase, and phosphatidylinositol 3-kinase signaling. E2 also altered the expression of genes linked to lipid synthesis and metabolism, vasoconstriction and vasodilation, cell-cell communication, and histone modification. These results demonstrate the far-reaching and diverse effects of E2 in the cerebral cortex and provide valuable insight to begin to understand cortical processes that may fluctuate in a dynamic hormonal environment.
Insights
17β-estradiol (E2) influences brain function by altering gene expression in the cerebral cortex. This study reveals E2
Area of Science:
- Neuroscience
- Endocrinology
- Molecular Biology
Background:
- 17β-estradiol (E2) is a key hormone with known effects on inflammation and ischemia in the brain.
- The precise molecular mechanisms underlying E2's actions in the cerebral cortex remain largely unknown.
Purpose of the Study:
- To investigate the molecular mechanisms of 17β-estradiol (E2) in the mouse cerebral cortex.
- To identify genes and pathways regulated by E2 in this brain region.
Main Methods:
- Ovariectomized adult female mice were treated with either oil (control) or E2.
- Cerebral cortical RNA was isolated and analyzed using RNA-sequencing after 7 days.
- Transcriptome analysis identified differentially expressed genes.
Main Results:
- E2 treatment significantly altered the expression of 88 genes in the cerebral cortex.
- Affected genes are involved in synaptic potentiation, myelination, and kinase signaling pathways (MAPK, PI3K).
- E2 also modulated genes related to lipid metabolism, vascular function, cell communication, and histone modification.
Conclusions:
- 17β-estradiol (E2) exerts widespread and diverse effects on the cerebral cortex transcriptome.
- These findings provide insights into E2's role in cortical processes within a dynamic hormonal environment.
- Understanding these mechanisms is crucial for neuroprotection and cognitive function.

