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dc.contributor.authorLee, Sophie N-
dc.contributor.authorKraska, Jenna-
dc.contributor.authorPapargiris, Melissa-
dc.contributor.authorTeng, Linda-
dc.contributor.authorNiranjan, Birunthi-
dc.contributor.authorHammar, Johanna-
dc.contributor.authorRyan, Andrew-
dc.contributor.authorFrydenberg, Mark-
dc.contributor.authorLawrentschuk, Nathan-
dc.contributor.authorMiddendorff, Ralf-
dc.contributor.authorEllem, Stuart J-
dc.contributor.authorWhittaker, Michael-
dc.contributor.authorRisbridger, Gail P-
dc.contributor.authorExintaris, Betty-
dc.identifier.citationScientific Reports 2021; 11(1): 6352en
dc.description.abstractPharmacotherapies for the treatment of Benign Prostatic Hyperplasia (BPH) are targeted at reducing cellular proliferation (static component) or reducing smooth muscle tone (dynamic component), but response is unpredictable and many patients fail to respond. An impediment to identifying novel pharmacotherapies is the incomplete understanding of paracrine signalling. Oxytocin has been highlighted as a potential paracrine mediator of BPH. To better understand oxytocin signalling, we investigated the effects of exogenous oxytocin on both stromal cell proliferation, and inherent spontaneous prostate contractions using primary models derived from human prostate tissue. We show that the Oxytocin Receptor (OXTR) is widely expressed in the human prostate, and co-localises to contractile cells within the prostate stroma. Exogenous oxytocin did not modulate prostatic fibroblast proliferation, but did significantly (p < 0.05) upregulate the frequency of spontaneous contractions in prostate tissue, indicating a role in generating smooth muscle tone. Application of atosiban, an OXTR antagonist, significantly (p < 0.05) reduced spontaneous contractions. Individual tissue responsiveness to both exogenous oxytocin (R2 = 0.697, p < 0.01) and atosiban (R2 = 0.472, p < 0.05) was greater in tissue collected from older men. Overall, our data suggest that oxytocin is a key regulator of inherent spontaneous prostate contractions, and targeting of the OXTR and associated downstream signalling is an attractive prospect in the development of novel BPH pharmacotherapies.en
dc.subjectBenign Prostatic Hyperplasiaen
dc.titleOxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate.en
dc.typeJournal Articleen
dc.identifier.journaltitleScientific Reportsen
dc.identifier.affiliationInstitute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, Giessen, Germanyen
dc.identifier.affiliationTissuPath, Melbourne, VIC, Australiaen
dc.identifier.affiliationEJ Whitten Prostate Cancer Research Centre at Epworth Heathcare, Melbourne, Australiaen
dc.identifier.affiliationDepartment of Surgery, Monash University, Melbourne, VIC, Australiaen
dc.identifier.affiliationAustralian Urology Associates, Melbourne, VIC, Australiaen
dc.identifier.affiliationDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Melbourne, VIC, 3052, Australiaen
dc.identifier.affiliationDepartment of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australiaen
dc.identifier.affiliationARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Faculty of Pharmacy and Pharmaceutical Sciences, Parkville, VIC, Australiaen
dc.identifier.affiliationSchool of Health and Wellbeing, Faculty of Health, Engineering and Sciences, University of Southern Queensland, Ipswich, QLD, Australiaen
dc.identifier.affiliationSurgery (University of Melbourne)en
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