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Sex differences in exercise-induced physiological myocardial hypertrophy are modulated by oestrogen receptor beta

Item Type:Article
Title:Sex differences in exercise-induced physiological myocardial hypertrophy are modulated by oestrogen receptor beta
Creators Name:Dworatzek, E. and Mahmoodzadeh, S. and Schubert, C. and Westphal, C. and Leber, J. and Kusch, A. and Kararigas, G. and Fliegner, D. and Moulin, M. and Ventura-Clapier, R. and Gustafsson, J.A. and Davidson, M.M. and Dragun, D. and Regitz-Zagrosek, V.
Abstract:AIMS: Oestrogen receptor alpha (ER{alpha}) and beta (ER{beta}) 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), ER{alpha}- and ER{beta}-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 ER{alpha}-deleted mice run less than female WT mice (P <= 0.001). ER{beta}-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, ER{beta} deletion abolished all observed sex differences. Mitochondrial remodelling occurred in female WT-VCR mice, but not in female ER{beta}-deleted mice. CONCLUSION: The sex-specific response of the heart to exercise is modulated by ER{beta}. The greater increase in physiological MH in females is mediated by induction of AKT signalling, MAPK pathways, protein synthesis, and mitochondrial adaptation via ER{beta}.
Keywords:Exercise-Induced Physiological MH, Sex, Oestrogen Receptor, Hypertrophy Associated, Signalling Pathway, Mitochondrial Adaptation, Animals, Mice
Source:Cardiovascular Research
ISSN:0008-6363
Publisher:Elsevier (The Netherlands)
Volume:102
Number:3
Page Range:418-428
Date:1 June 2014
Official Publication:https://doi.org/10.1093/cvr/cvu065
PubMed:View item in PubMed

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