Sex differences in exercise-induced physiological myocardial hypertrophy are modulated by oestrogen receptor beta
Abstract
AIMS: Oestrogen receptor alpha (ERα) and beta (ERβ) are involved in the regulation of pathological myocardial hypertrophy (MH). We hypothesize that both ER are also involved in physiological MH. Therefore, we investigated the role of ER in exercise-induced physiological MH in loss-of-function models and studied potential mechanisms of action. METHODS AND RESULTS: We performed 1 and 8 weeks of voluntary cage wheel running (VCR) with male and female C57BL/6J wild-type (WT), ERα- and ERβ-deleted mice. In line with other studies, female WT mice ran more than males (P ≤ 0.001). After 8 weeks of VCR, both sexes showed an increase in left ventricular mass (females: P ≤ 0.01 and males: P ≤ 0.05) with more pronounced MH in females (P < 0.05). As previously shown, female ERα-deleted mice run less than female WT mice (P ≤ 0.001). ERβ-deleted mice showed similar running performance as WT mice (females vs. male: P ≤ 0.001), but did not develop MH. Only female WT mice showed an increase in phosphorylation of serine/threonine kinase (AKT), ERK1/2, p38-mitogen-activated protein kinase (MAPK), and ribosomal protein s6, as well as an increase in the expression of key regulators of mitochondrial function and mitochondrial respiratory chain proteins (complexes I, III, and V) after VCR. However, ERβ deletion abolished all observed sex differences. Mitochondrial remodelling occurred in female WT-VCR mice, but not in female ERβ-deleted mice. CONCLUSION: The sex-specific response of the heart to exercise is modulated by ERβ. The greater increase in physiological MH in females is mediated by induction of AKT signalling, MAPK pathways, protein synthesis, and mitochondrial adaptation via ERβ.
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Female rodents show higher endurance capacities and anti-fatigue properties than male rodents.
“Additionally, previous studies have revealed that female rodents show higher endurance capacities and anti-fatigue properties than male rodents (107, 108).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [108]
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“Additionally, previous studies have revealed that female rodents show higher endurance capacities and anti-fatigue properties than male rodents (107, 108).”
Background
- Authors
- Dworatzek, E., Mahmoodzadeh, S., Schubert, C., Westphal, C., Leber, J., Kusch, A., Kararigas, G., Fliegner, D., Moulin, M., Ventura-Clapier, R., Gustafsson, J.-A., Davidson, M. M., Dragun, D., & Regitz-Zagrosek, V.
- Affiliations
- German Centre for Cardiovascular Research (DE)
- Max Delbrück Center (DE)
- Stiftung Charité (DE)
- Université Paris-Sud (FR)
- Columbia University (US)
- Corresponding author
- Dworatzek, Elke
- Venue
- Cardiovascular Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-03-19
- Volume
- 102
- Issue
- 3
- Pages
- 418-428
- ISSN
- 0008-6363 (ISSN-L)
- 1755-3245
- OpenAlex
- W2107134643
- Cited by
- 79
- References
- 58
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 1 · 2023: 7 · 2022: 8 · 2021: 8 · 2020: 8 · 2019: 10 · 2018: 4 · 2017: 6 · 2016: 9 · 2015: 8
- FWCI
- 5.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cardiovascular Research (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- estrogen receptor beta, estrogen receptor alpha, sex differences, left ventricular mass, mitochondrial remodeling, mitochondrial respiratory chain, Akt signaling, ERK1/2, p38 MAPK, ribosomal protein S6, protein synthesis, cardiac adaptation to exercise, ERβ knockout mice
- MeSH terms
- Adaptation, Physiological, Animals, Cells, Cultured, Female, Cardiomegaly, Male, Mice, Inbred C57BL, Mitochondria, Oxidative Phosphorylation, Physical Conditioning, Animal, Receptors, Estrogen, Sex Characteristics, Signal Transduction, MAP Kinase Signaling System, Estrogen Receptor beta, p38 Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-akt, Mice
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