Pro‐hypertrophic effect of 17β‐estradiol in the healthy heart

Studies in stressed or diseased hearts have shown anti‐hypertrophic actions of 17β‐estradiol (E2). However, little is known about E2 actions in the stress‐ and disease‐free heart. The aim of our study was to identify and characterize structurally and molecularly the role of E2 in the healthy heart. Female C57Bl/6J mice were ovariectomized at two months old and were fed on an E2‐containing ( n = 19) or soy‐free (Ctrl; n = 19) diet for three months. E2 led to an increase in the heart weight (11%; P < 0.001) and the heart‐to‐body weight ratio (32%; P < 0.001) compared to Ctrl mice. Cardiomyocyte cross‐sectional area revealed cardiomyocyte hypertrophy in E2 ( n = 6) compared to Ctrl ( n = 5) mice (32%; P = 0.004). Analysis of the left ventricular transcriptome identified 1059 probe sets (adjusted P ≤ 0.05) differentially expressed between E2 ( n = 5) and Ctrl ( n = 5). Hypergeometric testing for Gene Ontology showed most genes to be associated with cell cycle, regulation of growth, cell and tissue development. Pathway analysis revealed 140 pathways (1000 permutations; P = 0.05) modulated between the two groups, such as the DNA replication and Wnt signaling pathways. In conclusion, our study is the first to demonstrate the pro‐hypertrophic action of E2 in the healthy heart through the modulation of growth‐related genes and pathways. We believe this hypertrophic effect of E2 to be of the physiological type and beneficial for the heart.