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

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 nove...

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Autores principales:	Sophie N. Lee, Jenna Kraska, Melissa Papargiris, Linda Teng, Birunthi Niranjan, Johanna Hammar, Andrew Ryan, Mark Frydenberg, Nathan Lawrentschuk, Ralf Middendorff, Stuart J. Ellem, Michael Whittaker, Gail P. Risbridger, Betty Exintaris
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/35fdc4c338b54fd9a1b12af28ad3e9e2
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spelling	oai:doaj.org-article:35fdc4c338b54fd9a1b12af28ad3e9e22021-12-02T13:18:08ZOxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate10.1038/s41598-021-85439-42045-2322https://doaj.org/article/35fdc4c338b54fd9a1b12af28ad3e9e22021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85439-4https://doaj.org/toc/2045-2322Abstract 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.Sophie N. LeeJenna KraskaMelissa PapargirisLinda TengBirunthi NiranjanJohanna HammarAndrew RyanMark FrydenbergNathan LawrentschukRalf MiddendorffStuart J. EllemMichael WhittakerGail P. RisbridgerBetty ExintarisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sophie N. Lee Jenna Kraska Melissa Papargiris Linda Teng Birunthi Niranjan Johanna Hammar Andrew Ryan Mark Frydenberg Nathan Lawrentschuk Ralf Middendorff Stuart J. Ellem Michael Whittaker Gail P. Risbridger Betty Exintaris Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate
description	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.
format	article
author	Sophie N. Lee Jenna Kraska Melissa Papargiris Linda Teng Birunthi Niranjan Johanna Hammar Andrew Ryan Mark Frydenberg Nathan Lawrentschuk Ralf Middendorff Stuart J. Ellem Michael Whittaker Gail P. Risbridger Betty Exintaris
author_facet	Sophie N. Lee Jenna Kraska Melissa Papargiris Linda Teng Birunthi Niranjan Johanna Hammar Andrew Ryan Mark Frydenberg Nathan Lawrentschuk Ralf Middendorff Stuart J. Ellem Michael Whittaker Gail P. Risbridger Betty Exintaris
author_sort	Sophie N. Lee
title	Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate
title_short	Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate
title_full	Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate
title_fullStr	Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate
title_full_unstemmed	Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate
title_sort	oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/35fdc4c338b54fd9a1b12af28ad3e9e2
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Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate

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