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

Lee, Sophie N. and Kraska, Jenna and Papargiris, Melissa and Teng, Lind and Niranjan, Birunthi and Hammar, Johanna and Ryan, Andrew and Frydenberg, Mark and Lawrentschuk, Nathan and Middendorff, Ralf and Ellem, Stuart J. and Whittaker, Michael and 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, 11:6352. pp. 1-11. ISSN 2045-2322

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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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing (1 Jan 2015 -)
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing (1 Jan 2015 -)
Date Deposited: 19 Mar 2021 01:19
Last Modified: 19 Mar 2021 01:19
Uncontrolled Keywords: Benign Prostatic Hyperplasia (BPH); treatment; pharmacotherapies; paracrine signalling; paracrine mediators; oxytocin
Fields of Research (2008): 11 Medical and Health Sciences > 1103 Clinical Sciences > 110312 Nephrology and Urology
11 Medical and Health Sciences > 1115 Pharmacology and Pharmaceutical Sciences > 111501 Basic Pharmacology
Fields of Research (2020): 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320214 Nephrology and urology
32 BIOMEDICAL AND CLINICAL SCIENCES > 3214 Pharmacology and pharmaceutical sciences > 321401 Basic pharmacology
Socio-Economic Objectives (2008): C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920119 Urogenital System and Disorders
C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920114 Reproductive System and Disorders
Socio-Economic Objectives (2020): 20 HEALTH > 2001 Clinical health > 200199 Clinical health not elsewhere classified
20 HEALTH > 2099 Other health > 209999 Other health not elsewhere classified
20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions
Identification Number or DOI: https://doi.org/10.1038/s41598-021-85439-4
URI: http://eprints.usq.edu.au/id/eprint/41579

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