Background and objective
Our patient cohort revealed that obesity is strongly associated with steroid-5α reductase type 2 (SRD5A2) promoter methylation and reduced protein expression. The underlying mechanism of prostatic growth in this population is poorly understood. Here we addressed the question of how obesity, inflammation, and steroid hormones affect the development of benign prostatic hyperplasia (BPH).
Material and methods
We used preadipocytes, macrophages, primary human prostatic stromal cells, prostate tissues from high-fat diet-induced obese mice, and 35 prostate specimens that were collected from patients who underwent transurethral resection of the prostate (TURP). RNA was isolated and quantified with RT-PCR. Genome DNA was extracted and SRD5A2 promoter methylation was determined. Sex hormones were determined by high-performance liquid chromatography–tandem mass spectrometry. Protein was extracted and determined by ELISA test.
In prostatic tissues with obesity, the levels of inflammatory mediators were elevated. SRD5A2 promoter methylation was promoted, but SRD5A2 expression was inhibited. Inflammatory mediators and saturated fatty acid synergistically regulated aromatase activity. Obesity promoted an androgenic to estrogenic switch in the prostate.
Our findings suggest that obesity-associated inflammation induces androgenic to estrogenic switch in the prostate gland, which may serve as an effective strategy for alternative therapies for management of lower urinary tract symptoms associated with BPH in select individuals.
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AFO gratefully acknowledges financial support from NIH/NIDDK (NIH/R01 DK091353). ZW was supported by the Urology Care Foundation/American Urological Association Research Scholar Award. We gratefully thank Dr Li Xin at University of Washington for supplying prostate tissues of mice fed with HFD or RFD.
Conflict of interest
The authors declare that they have no conflict of interest.
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Xue, B., Wu, S., Sharkey, C. et al. Obesity-associated inflammation induces androgenic to estrogenic switch in the prostate gland. Prostate Cancer Prostatic Dis (2020). https://doi.org/10.1038/s41391-020-0208-4
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