Journal
JOURNAL OF ENDOCRINOLOGY
Volume 197, Issue 3, Pages 493-501Publisher
SOC ENDOCRINOLOGY
DOI: 10.1677/JOE-08-0071
Keywords
-
Categories
Funding
- British Heart Foundation [FS/03/114, FS/05/119] Funding Source: Medline
Ask authors/readers for more resources
Oestrogen protects the heart from ischaemic injury. The current study aims to characterise two novel oestrogen receptor (ER) ligands, an ER alpha agonist ERA-45 and an ER beta antagonist ERB-88, and then use them to investigate the roles of ERa and ER beta in mediating the cardioprotection by E from ischaemia-reperfusion injury in the rat. The ER ligands were characterised by gene transactivation assay using ER-transfected Chinese hamster ovary (CHO) cells and in bioavailability studies in vivo. Female rats (n=48) were ovariectomised and implanted with 17 beta-oestradiol (17 beta E-2) releasing or placebo pellets. ERA-45, ERB-88 or vehicle was administered for 5 days prior to ischaemia-reperfusion studies. Necrosis, neutrophil infiltration (myeloperoxidase activity) and oxidant stress production (electron paramagnetic resonance) from the area-at-risk were measured to assess reperfusion injury. The ERA alpha agonist ERA-45 showed more than 35-fold selectivity for ERA compared with ER beta gene transactivation. In vitro, the ER beta antagonist ERB-88 inhibited transactivation by 17 beta E-2 via ER beta with 46-fold selectivity relative to inhibition via ER alpha. In vivo, 17 beta E-2 significantly reduced neutrophil infiltration, oxidant stress and necrosis following ischaemia and reperfusion. Cardioprotection by 17 beta E-2 was not inhibited by ERB-88 but was completely reproduced by ERA-45. In conclusion, protection of the rat heart after ischaemia-reperfusion by 17 beta E-2 is achieved through the reduction of cardiomyocyte death, neutrophil infiltration and oxygen-free radical availability. The results of this study indicate that these effects are primarily mediated via activation of ERA.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available