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Estrogen Receptor Regulation of the Heart in an Animal Model of Menopause and a Comparison of the Sex Differences

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dc.contributor.advisor Pyle, Glen Fernandes, Rosephine Del 2018-12-12T18:20:05Z 2019-10-23T05:00:34Z 2018-10 2018-10-23 2018-12-12
dc.description.abstract No study has examined the chronological myocardial changes associated with menopause. 4-vinylcyclohexene diepoxide (VCD) injection of female CD-1 mice caused accelerated ovarian follicular atresia over 120 d. Contractility declined with 15 min ER-alpha (4,4’,4”-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol, PPT, 100 nM) and ER-beta (diarylpropionitrile, DPN, 1 nM) agonist perfusion in intact hearts. ERα- and ERβ-dependent decreases in contractility were attenuated 60-days post-VCD (analogous to perimenopause). 120-days post-VCD (analogous to end of menopause) ERα-regulation was normalized whereas ERβ-control remained attenuated. Sex differences in ER functional response were not observed. Myofilament function was altered non-linearly during peri-menopause in conjunction with myofilament protein phosphorylation. Ovarian failure promoted a pro-inflammatory and pro-apoptotic state. We are the first to show the rapid effects of ER on myocardial function and their mechanisms of action are altered early in menopause. The non-linear changes in the heart during menopause may help explain the paradoxical findings of hormone replacement therapy clinical trials. en_US
dc.description.sponsorship Ontario Veterinary College. Ontario Graduate Fellowship. School of Graduate Studies. NSERC. CIHR. en_US
dc.language.iso en en_US
dc.publisher University of Guelph en_US
dc.subject cardiology en_US
dc.subject molecular cardiology en_US
dc.subject estrogen receptor en_US
dc.subject myocardium en_US
dc.subject menopause en_US
dc.subject VCD en_US
dc.subject timing hypothesis en_US
dc.subject sex differences en_US
dc.subject ovarian failure en_US
dc.title Estrogen Receptor Regulation of the Heart in an Animal Model of Menopause and a Comparison of the Sex Differences en_US
dc.type Thesis en_US Biomedical Sciences en_US Master of Science en_US Department of Biomedical Sciences en_US
dc.rights.license All items in the Atrium are protected by copyright with all rights reserved unless otherwise indicated. University of Guelph en_US

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