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

Bichen Xue, Shulin Wu, Christina Sharkey, Shahin Tabatabaei, Chin Lee Wu, Zhipeng Tao, Zhiyong Cheng, Douglas Strand, Aria F. Olumi, Zongwei Wang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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. 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.

Original languageEnglish (US)
Pages (from-to)465-474
Number of pages10
JournalProstate Cancer and Prostatic Diseases
Volume23
Issue number3
DOIs
StatePublished - Sep 1 2020

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

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