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Updated: May 23, 2026
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Estrogen and the cardiovascular system
1Molecular and Cellular Cardiology, Department of Medicine, University of California, Davis, CA 95616, USA. aaknowlton@ucdavis.edu
Abstract:
Estrogen is a potent steroid with pleiotropic effects, which have yet to be fully elucidated. Estrogen has both nuclear and non-nuclear effects. The rapid response to estrogen, which involves a membrane associated estrogen receptor(ER) and is protective, involves signaling through PI3K, Akt, and ERK 1/2. The nuclear response is much slower, as the ER-estrogen complex moves to the nucleus, where it functions as a transcription factor, both activating and repressing gene expression. Several different ERs regulate the specificity of response to estrogen, and appear to have specific effects in cardiac remodeling and the response to injury. However, much remains to be understood about the selectivity of these receptors and their specific effects on gene expression. Basic studies have demonstrated that estrogen treatment prevents apoptosis and necrosis of cardiac and endothelial cells. Estrogen also attenuates pathologic cardiac hypertrophy. Estrogen may have great benefit in aging as an anti-inflammatory agent. However, clinical investigations of estrogen have had mixed results, and not shown the clear-cut benefit of more basic investigations. This can be explained in part by differences in study design: in basic studies estrogen treatment was used immediately or shortly after ovariectomy, while in some key clinical trials, estrogen was given years after menopause. Further basic research into the underlying molecular mechanisms of estrogen's actions is essential to provide a better comprehension of the many properties of this powerful hormone.
Insights
Estrogen exerts rapid, membrane-initiated protective effects and slower nuclear actions influencing gene expression. Understanding estrogen
Area of Science:
- Endocrinology
- Molecular Biology
- Cardiovascular Science
Background:
- Estrogen is a steroid hormone with diverse physiological effects.
- Estrogen acts through both membrane-associated and nuclear receptors.
- Its roles in cellular protection and cardiac function are complex and not fully understood.
Purpose of the Study:
- To elucidate the pleiotropic effects of estrogen.
- To differentiate between rapid non-nuclear and slower nuclear estrogen signaling pathways.
- To explore the specific roles of different estrogen receptors (ERs) in cardiac remodeling and injury response.
Main Methods:
- Investigated rapid signaling pathways involving membrane-associated ERs, PI3K, Akt, and ERK 1/2.
- Examined slower, nuclear actions of the ER-estrogen complex as a transcription factor.
- Reviewed basic and clinical studies on estrogen's effects on cardiac and endothelial cells, apoptosis, necrosis, and hypertrophy.
Main Results:
- Estrogen demonstrates rapid, protective effects via membrane receptors and signaling cascades.
- Nuclear ER-estrogen complexes modulate gene expression, affecting cardiac remodeling.
- Basic studies show estrogen prevents cell death and attenuates cardiac hypertrophy, suggesting anti-inflammatory benefits.
- Clinical trial results for estrogen have been mixed, potentially due to timing of administration relative to menopause.
Conclusions:
- Estrogen possesses multifaceted actions, including rapid cellular protection and slower gene regulation.
- Specific estrogen receptors (ERs) mediate distinct effects in the cardiovascular system.
- Further research into molecular mechanisms is crucial for understanding estrogen's therapeutic potential, especially considering discrepancies between basic and clinical findings regarding timing of intervention.
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