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  • Sir Peter MacCallum Department of Oncology
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    Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS.

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    Author
    Nesheim, N; Ellem, S; Dansranjavin, T; Hagenkötter, C; Berg, E; Schambeck, R; Schuppe, H-C; Pilatz, A; Risbridger, G; Weidner, W; ...
    Date
    2018-04-13
    Source Title
    Oncotarget
    Publisher
    Impact Journals, LLC
    University of Melbourne Author/s
    Risbridger, Gail
    Affiliation
    Sir Peter MacCallum Department of Oncology
    Metadata
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    Document Type
    Journal Article
    Citations
    Nesheim, 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.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/254855
    DOI
    10.18632/oncotarget.24714
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929413
    Abstract
    Chronic 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.

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