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dc.contributor.authorNesheim, N
dc.contributor.authorEllem, S
dc.contributor.authorDansranjavin, T
dc.contributor.authorHagenkötter, C
dc.contributor.authorBerg, E
dc.contributor.authorSchambeck, R
dc.contributor.authorSchuppe, H-C
dc.contributor.authorPilatz, A
dc.contributor.authorRisbridger, G
dc.contributor.authorWeidner, W
dc.contributor.authorWagenlehner, F
dc.contributor.authorSchagdarsurengin, U
dc.date.accessioned2020-12-17T03:22:02Z
dc.date.available2020-12-17T03:22:02Z
dc.date.issued2018-04-13
dc.identifierpii: 24714
dc.identifier.citationNesheim, N., Ellem, S., Dansranjavin, T., Hagenkötter, C., Berg, E., Schambeck, R., Schuppe, H. -C., Pilatz, A., Risbridger, G., Weidner, W., Wagenlehner, F. & Schagdarsurengin, U. (2018). Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS.. Oncotarget, 9 (28), pp.19623-19639. https://doi.org/10.18632/oncotarget.24714.
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/11343/254855
dc.description.abstractChronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is associated with urinary tract symptoms and hormonal imbalances amongst others. The heterogeneous clinical presentation, unexplored molecular background and lack of prostate biopsies complicate therapy. Here, using liquid biopsies, we performed a comprehensive translational study on men diagnosed with CP/CPPS type III (n = 50; median age 39.8, range 23-65) and age-matched controls (n = 61; median age 36.8, range 20-69), considering biochemical parameters of blood and ejaculates, and epigenetic regulation of the estrogen receptor genes (ESR1 and ESR2) in leukocytes isolated from blood (systemic regulation) and in somatic cells isolated from ejaculates (local regulation). We found elevated 17β-estradiol (E2) levels in seminal plasma, but not in blood plasma, that was significantly associated with CP/CPPS and impaired urinary tract symptoms. In ejaculated somatic cells of CP/CPPS patients we found that ESR1 and ESR2 were both significantly higher methylated in CpG-promoters and expressionally down-regulated in comparison to controls. Mast cells are reported to contribute to CP/CPPS and are estrogen responsive. Consistent with this, we found that E2 -treatment of human mast cell lines (HMC-1 and LAD2) resulted in altered cytokine and chemokine expression. Interestingly, in HMC-1 cells, possessing epigenetically inactivated ESR1 and ESR2, E2 -treatment led to a reduced transcription of a number of inflammatory genes. Overall, these data suggest that elevated local E2 levels associate with an epigenetic down-regulation of the estrogen receptors and have a prominent role in CP/CPPS. Investigating E2 levels in semen could therefore serve as a promising biomarker to select patients for estrogen targeted therapy.
dc.languageeng
dc.publisherImpact Journals, LLC
dc.titleElevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS.
dc.typeJournal Article
dc.identifier.doi10.18632/oncotarget.24714
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.source.titleOncotarget
melbourne.source.volume9
melbourne.source.issue28
melbourne.source.pages19623-19639
dc.rights.licenseCC BY
melbourne.elementsid1323973
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929413
melbourne.contributor.authorRisbridger, Gail
dc.identifier.eissn1949-2553
melbourne.accessrightsOpen Access


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