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Obesity-associated inflammation induces androgenic to estrogenic switch in the prostate gland.


ABSTRACT:

Background and objective

Our patient cohort revealed that obesity is strongly associated with steroid-5? 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.

Results

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.

Conclusions

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.

SUBMITTER: Xue B 

PROVIDER: S-EPMC7938647 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Obesity-associated inflammation induces androgenic to estrogenic switch in the prostate gland.

Xue Bichen B   Wu Shulin S   Sharkey Christina C   Tabatabaei Shahin S   Wu Chin-Lee CL   Tao Zhipeng Z   Cheng Zhiyong Z   Strand Douglas D   Olumi Aria F AF   Wang Zongwei Z  

Prostate cancer and prostatic diseases 20200206 3


<h4>Background and objective</h4>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).<h4>Material and methods</h4>We used preadipocytes, macrophages, primary human  ...[more]

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