Aim: 

The direct influence of 17b-estradiol (E2) on the male heart has received little attention, even though multidisciplinary data have revealed E2-induced cardiovascular actions. Both genomic and nongenomic effects of E2 require activation of the estrogen receptor (ER) a and ERb. Recently, a novel membrane G protein-coupled receptor, named GPR30, has been implicated in rapid E2 signaling. We aimed to investigate the influence of E2 on the performance of the mammalian male heart and the molecular mechanisms involved.

Methods: 

The E2 cardiotropic effect was evaluated using the isolated, Langendorff perfused male Wistar rat heart. The expression of ERa, ERb and GPR30 at both mRNA and protein levels were assessed through reverse-transcription PCR and western blotting. cGMP concentration was evaluated by EIA assay.

Results: 

E2 negatively affected cardiac performance through a dose-dependent reduction of contractility. This action, was mimicked by selective agonists for ERa and ERb, and blocked by the ER inhibitor ICI 182,780. The putative role of GPR30 was demonstrated by using the selective ligand G-1. Moreover, E2-induced cardiac responses involved ERK, PI3K, PKA, and eNOS transduction pathways.

Conclusions: 

Taken together these data suggest that the cardiotropic effect of E2 in the male rat heart is not only mediated by ERa and ERb, but also by GPR30 signaling.