Upregulation of Oxytocin Receptor in the Hyperplastic Prostate
Background: The etiology of benign prostatic hyperplasia (BPH) is complex, both age and androgen are thought to be important. However, the failure of androgen blockade treatments suggests other paracrine/autocrine factors involved in BPH. Oxytocin was found to have a paracrine/autocrine role in pros...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2018.00403/full |
| _version_ | 1819071509016084480 |
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| author | Zhuo Li Zhuo Li He Xiao Kebing Wang Yuelan Zheng Ping Chen Xinghuan Wang Michael E. DiSanto Xinhua Zhang |
| author_facet | Zhuo Li Zhuo Li He Xiao Kebing Wang Yuelan Zheng Ping Chen Xinghuan Wang Michael E. DiSanto Xinhua Zhang |
| author_sort | Zhuo Li |
| collection | DOAJ |
| description | Background: The etiology of benign prostatic hyperplasia (BPH) is complex, both age and androgen are thought to be important. However, the failure of androgen blockade treatments suggests other paracrine/autocrine factors involved in BPH. Oxytocin was found to have a paracrine/autocrine role in prostate in recent years. The influence of BPH on prostatic oxytocin receptor (OTR) expression has never been studied.Material and methods: A testosterone-estradiol induced rat model of BPH was employed and human hyperplastic prostate specimens were harvested. Expressions of OTR, α1-adrenoreceptor subtypes and nitric oxide synthase isoforms were determined via real-time RT-PCR. OTR was further analyzed with Western-Blotting and histological examination. Subsequently, rat epithelial cells, human stromal cells and epithelial cells were cultured in vitro and treated with gradient concentrations of OT from 1 to 5 days. Cell proliferation was tested by Cell Counting Kit-8 and Flow Cytometry.Results: The rat BPH model was validated with significant increased prostate weight. H-E stain revealed a different histopathology between human and rat BPH. Masson's trichrome staining demonstrated that smooth muscle (SM) cells, epithelium cells and collagen fibers were simultaneously augmented in this rat BPH model and human BPH samples. OTR mainly localized in epithelium in rat prostate whereas it mainly localized in stroma in human prostate. OTR gene was upregulated 3.3-fold in rat BPH and 3.0-fold in human BPH, along with increased expression of 2.0-fold α1aARs and 3.0-fold eNOS for rat BPH and 5.0-fold α1aARs for human BPH. The expression of OTR protein was upregulated 1.4-fold in rat BPH and 3.9-fold in human BPH, respectively. Increased concentrations of exogenous OT can accelerate proliferation of rat epithelial cells and human stromal cells but has no impact on human epithelial cells in vitro. Flow Cytometry showed oxytocin could significantly increase G2/M period cell number.Conclusions: Our novel data demonstrates a significant and previously undocumented upregulation of OTR in both rat and human BPH. Moreover, exogenous OT accelerates proliferation of rat prostate epithelial cells and human prostate stromal cells. It is suggested OTR is involved in the development of BPH and OT regulatory system could be a potential new target for the BPH treatment. |
| first_indexed | 2024-12-21T17:22:57Z |
| format | Article |
| id | doaj.art-c0a1d06322b943e5bb5fed9880d0b34c |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-21T17:22:57Z |
| publishDate | 2018-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-c0a1d06322b943e5bb5fed9880d0b34c2022-12-21T18:56:07ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-08-01910.3389/fendo.2018.00403378182Upregulation of Oxytocin Receptor in the Hyperplastic ProstateZhuo Li0Zhuo Li1He Xiao2Kebing Wang3Yuelan Zheng4Ping Chen5Xinghuan Wang6Michael E. DiSanto7Xinhua Zhang8Zhongnan Hospital of Wuhan University, Wuhan, ChinaShenzhen Key Laboratory for Endogenous Infection, Department of Urology, Shenzhen Sixth People's Hospital, The Sixth Affiliated Hospital of Shenzhen University Health Science Center, Affiliated Shenzhen Sixth Hospital of Guangdong Medical University, Shenzhen, ChinaZhongnan Hospital of Wuhan University, Wuhan, ChinaShenzhen Key Laboratory for Endogenous Infection, Department of Urology, Shenzhen Sixth People's Hospital, The Sixth Affiliated Hospital of Shenzhen University Health Science Center, Affiliated Shenzhen Sixth Hospital of Guangdong Medical University, Shenzhen, ChinaDepartment of General Surgery, Children's Hospital of Shenzhen, Shenzhen, ChinaZhongnan Hospital of Wuhan University, Wuhan, ChinaZhongnan Hospital of Wuhan University, Wuhan, ChinaDepartments of Biomedical Sciences, Surgery of Cooper Medical School of Rowan University, Camden, NJ, United StatesZhongnan Hospital of Wuhan University, Wuhan, ChinaBackground: The etiology of benign prostatic hyperplasia (BPH) is complex, both age and androgen are thought to be important. However, the failure of androgen blockade treatments suggests other paracrine/autocrine factors involved in BPH. Oxytocin was found to have a paracrine/autocrine role in prostate in recent years. The influence of BPH on prostatic oxytocin receptor (OTR) expression has never been studied.Material and methods: A testosterone-estradiol induced rat model of BPH was employed and human hyperplastic prostate specimens were harvested. Expressions of OTR, α1-adrenoreceptor subtypes and nitric oxide synthase isoforms were determined via real-time RT-PCR. OTR was further analyzed with Western-Blotting and histological examination. Subsequently, rat epithelial cells, human stromal cells and epithelial cells were cultured in vitro and treated with gradient concentrations of OT from 1 to 5 days. Cell proliferation was tested by Cell Counting Kit-8 and Flow Cytometry.Results: The rat BPH model was validated with significant increased prostate weight. H-E stain revealed a different histopathology between human and rat BPH. Masson's trichrome staining demonstrated that smooth muscle (SM) cells, epithelium cells and collagen fibers were simultaneously augmented in this rat BPH model and human BPH samples. OTR mainly localized in epithelium in rat prostate whereas it mainly localized in stroma in human prostate. OTR gene was upregulated 3.3-fold in rat BPH and 3.0-fold in human BPH, along with increased expression of 2.0-fold α1aARs and 3.0-fold eNOS for rat BPH and 5.0-fold α1aARs for human BPH. The expression of OTR protein was upregulated 1.4-fold in rat BPH and 3.9-fold in human BPH, respectively. Increased concentrations of exogenous OT can accelerate proliferation of rat epithelial cells and human stromal cells but has no impact on human epithelial cells in vitro. Flow Cytometry showed oxytocin could significantly increase G2/M period cell number.Conclusions: Our novel data demonstrates a significant and previously undocumented upregulation of OTR in both rat and human BPH. Moreover, exogenous OT accelerates proliferation of rat prostate epithelial cells and human prostate stromal cells. It is suggested OTR is involved in the development of BPH and OT regulatory system could be a potential new target for the BPH treatment.https://www.frontiersin.org/article/10.3389/fendo.2018.00403/fulloxytocinreceptorprostatebenign prostatic hyperplasiaandrogenestrogen |
| spellingShingle | Zhuo Li Zhuo Li He Xiao Kebing Wang Yuelan Zheng Ping Chen Xinghuan Wang Michael E. DiSanto Xinhua Zhang Upregulation of Oxytocin Receptor in the Hyperplastic Prostate Frontiers in Endocrinology oxytocin receptor prostate benign prostatic hyperplasia androgen estrogen |
| title | Upregulation of Oxytocin Receptor in the Hyperplastic Prostate |
| title_full | Upregulation of Oxytocin Receptor in the Hyperplastic Prostate |
| title_fullStr | Upregulation of Oxytocin Receptor in the Hyperplastic Prostate |
| title_full_unstemmed | Upregulation of Oxytocin Receptor in the Hyperplastic Prostate |
| title_short | Upregulation of Oxytocin Receptor in the Hyperplastic Prostate |
| title_sort | upregulation of oxytocin receptor in the hyperplastic prostate |
| topic | oxytocin receptor prostate benign prostatic hyperplasia androgen estrogen |
| url | https://www.frontiersin.org/article/10.3389/fendo.2018.00403/full |
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