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dc.contributor.authorLee, SN
dc.contributor.authorKraska, J
dc.contributor.authorPapargiris, M
dc.contributor.authorTeng, L
dc.contributor.authorNiranjan, B
dc.contributor.authorHammar, J
dc.contributor.authorRyan, A
dc.contributor.authorFrydenberg, M
dc.contributor.authorLawrentschuk, N
dc.contributor.authorMiddendorff, R
dc.contributor.authorEllem, SJ
dc.contributor.authorWhittaker, M
dc.contributor.authorRisbridger, GP
dc.contributor.authorExintaris, B
dc.date.accessioned2021-05-04T00:46:57Z
dc.date.available2021-05-04T00:46:57Z
dc.date.issued2021-03-18
dc.identifierpii: 10.1038/s41598-021-85439-4
dc.identifier.citationLee, S. N., Kraska, J., Papargiris, M., Teng, L., Niranjan, B., Hammar, J., Ryan, A., Frydenberg, M., Lawrentschuk, N., Middendorff, R., Ellem, S. J., Whittaker, M., Risbridger, G. P. & Exintaris, B. (2021). Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate. SCIENTIFIC REPORTS, 11 (1), https://doi.org/10.1038/s41598-021-85439-4.
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/11343/273212
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.
dc.languageEnglish
dc.publisherNATURE RESEARCH
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleOxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate
dc.typeJournal Article
dc.identifier.doi10.1038/s41598-021-85439-4
melbourne.affiliation.departmentSurgery (Austin & Northern Health)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleScientific Reports
melbourne.source.volume11
melbourne.source.issue1
melbourne.source.pages6352-
dc.rights.licenseCC BY
melbourne.elementsid1507258
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973579
melbourne.contributor.authorLawrentschuk, Nathan
melbourne.contributor.authorRisbridger, Gail
dc.identifier.eissn2045-2322
melbourne.accessrightsOpen Access


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