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Title: Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate.
Austin Authors: Lee, Sophie N;Kraska, Jenna;Papargiris, Melissa;Teng, Linda;Niranjan, Birunthi;Hammar, Johanna;Ryan, Andrew;Frydenberg, Mark;Lawrentschuk, Nathan;Middendorff, Ralf;Ellem, Stuart J;Whittaker, Michael;Risbridger, Gail P;Exintaris, Betty
Affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, Giessen, Germany
TissuPath, Melbourne, VIC, Australia
EJ Whitten Prostate Cancer Research Centre at Epworth Heathcare, Melbourne, Australia
Department of Surgery, Monash University, Melbourne, VIC, Australia
Australian Urology Associates, Melbourne, VIC, Australia
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Melbourne, VIC, 3052, Australia
Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Faculty of Pharmacy and Pharmaceutical Sciences, Parkville, VIC, Australia
School of Health and Wellbeing, Faculty of Health, Engineering and Sciences, University of Southern Queensland, Ipswich, QLD, Australia
Surgery (University of Melbourne)
Issue Date: 18-Mar-2021 2021-03-18
Publication information: Scientific Reports 2021; 11(1): 6352
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.
DOI: 10.1038/s41598-021-85439-4
PubMed URL: 33737570
Type: Journal Article
Subjects: Pharmacotherapy
Benign Prostatic Hyperplasia
Appears in Collections:Journal articles

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