Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS

Nesheim, Nils and Ellem, Stuart and Dansranjavin, Temuujin and Kagenkotter, Christina and Berg, Elena and Schambeck, Rupert and Schuppe, Hans-Christian and Pilatz, Adrian and Risbridger, Gail and Weidner, Wolfgang and Wagenlehner, Florian and Schagdarsurengin, Undraga (2018) Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS. Oncotarget, 9 (28). pp. 19623-19639.

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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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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Licensed under a Creative Commons Attribution 3.0 License.
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: 16 Dec 2019 07:49
Last Modified: 03 Jan 2020 01:15
Uncontrolled Keywords: chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); epigenetic inactivation; estradiol; estrogene receptor; liquid biopsies
Fields of Research : 11 Medical and Health Sciences > 1103 Clinical Sciences > 110312 Nephrology and Urology
11 Medical and Health Sciences > 1114 Paediatrics and Reproductive Medicine > 111499 Paediatrics and Reproductive Medicine not elsewhere classified
Socio-Economic Objective: 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) > 920106 Endocrine Organs and Diseases (excl. Diabetes)
Identification Number or DOI: doi:10.18632/oncotarget.24714
URI: http://eprints.usq.edu.au/id/eprint/35870

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