Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate

Article


Lee, Sophie N., Kraska, Jenna, Papargiris, Melissa, Teng, Lind, Niranjan, Birunthi, Hammar, Johanna, Ryan, Andrew, Frydenberg, Mark, Lawrentschuk, Nathan, Middendorff, Ralf, Ellem, Stuart J., Whittaker, Michael, Risbridger, Gail P. and Exintaris, Betty. 2021. "Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate." Scientific Reports. 11, pp. 1-11. https://doi.org/10.1038/s41598-021-85439-4
Article Title

Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate

ERA Journal ID201487
Article CategoryArticle
AuthorsLee, Sophie N. (Author), Kraska, Jenna (Author), Papargiris, Melissa (Author), Teng, Lind (Author), Niranjan, Birunthi (Author), Hammar, Johanna (Author), Ryan, Andrew (Author), Frydenberg, Mark (Author), Lawrentschuk, Nathan (Author), Middendorff, Ralf (Author), Ellem, Stuart J. (Author), Whittaker, Michael (Author), Risbridger, Gail P. (Author) and Exintaris, Betty (Author)
Journal TitleScientific Reports
Journal Citation11, pp. 1-11
Article Number6352
Number of Pages11
Year2021
PublisherNature Publishing Group
Place of PublicationUnited Kingdom
ISSN2045-2322
Digital Object Identifier (DOI)https://doi.org/10.1038/s41598-021-85439-4
Web Address (URL)https://www.nature.com/articles/s41598-021-85439-4
Abstract

Pharmacotherapies 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.

KeywordsBenign Prostatic Hyperplasia (BPH); treatment; pharmacotherapies; paracrine signalling; paracrine mediators; oxytocin
ANZSRC Field of Research 2020320214. Nephrology and urology
321401. Basic pharmacology
Byline AffiliationsMonash University
TissuPath, Australia
University of Melbourne
Justus Liebig-University Giessen, Germany
School of Health and Wellbeing
Institution of OriginUniversity of Southern Queensland
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