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

dc.contributor.advisorPyle, Glen
dc.contributor.authorFernandes, Rosephine Del
dc.date.accessioned2018-12-12T18:20:05Z
dc.date.available2019-10-23T05:00:34Z
dc.date.copyright2018-10
dc.date.created2018-10-23
dc.date.issued2018-12-12
dc.degree.departmentDepartment of Biomedical Sciencesen_US
dc.degree.grantorUniversity of Guelphen_US
dc.degree.nameMaster of Scienceen_US
dc.degree.programmeBiomedical Sciencesen_US
dc.description.abstractNo 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.sponsorshipOntario Veterinary College
dc.description.sponsorshipOntario Graduate Fellowship
dc.description.sponsorshipSchool of Graduate Studies
dc.description.sponsorshipNatural Sciences and Engineering Research Council of Canada
dc.description.sponsorshipCIHR
dc.identifier.urihttp://hdl.handle.net/10214/14608
dc.language.isoenen_US
dc.publisherUniversity of Guelphen_US
dc.rights.licenseAll items in the Atrium are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectcardiologyen_US
dc.subjectmolecular cardiologyen_US
dc.subjectestrogen receptoren_US
dc.subjectmyocardiumen_US
dc.subjectmenopauseen_US
dc.subjectVCDen_US
dc.subjecttiming hypothesisen_US
dc.subjectsex differencesen_US
dc.subjectovarian failureen_US
dc.titleEstrogen Receptor Regulation of the Heart in an Animal Model of Menopause and a Comparison of the Sex Differencesen_US
dc.typeThesisen_US

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