Abstract

Benign prostatic hyperplasia (BPH) is one of the major public health concerns, which has a high prevalence rate and causes significant decline in men’s quality of life. BPH is highly related to sexual hormone metabolism and aging. In particular, dihydrotestosterone (DHT), to which testosterone is modified by 5α-reductase (5AR), has a significant effect on BPH development. DHT binds to an androgen receptor (AR) and steroid receptor coactivator 1 (SRC-1); then, it induces the proliferation of a prostate cell and expression of prostate specific antigen (PSA). Paecilomyces tenuipes (P. tenuipes) is a mushroom that has been popularized by the artificial cultivation of fruiting bodies based on silkworms by researchers from the Republic of Korea. In a previous study, we identified the effect of PE on PSA mRNA expression in LNCaP cells. This suggests that PE may have an inhibitory effect on androgen signaling. Therefore, we confirmed the expression of androgen signaling-related factors, such as AR, SRC-1, and PSA in LNCaP. Furthermore, we confirmed the androgen signaling inhibitory effect of PE using the testosterone propionate (TP)-induced BPH rat model. A BPH rat model was established with a four-week treatment of daily subcutaneous injections of testosterone propionate (TP, 3 mg/kg) dissolved in corn oil after castration. The rats in the treatment group were orally gavaged P. tenuipes extract (PE), finasteride (Fi), or saw palmetto extract (Saw) with TP injection. DHT induced an increase in the expression levels of AR, SRC-1, and PSA proteins in LNCaP cells. On the contrary, the PE treatment reduced the expression levels. In vivo, the BPH group showed an increase in prostate size compared with the control group. The PE gavaged group showed a decrease in prostate size compared with the BPH group. In addition, the protein expressions of AR, 5AR2, and PSA were significantly lower in the PE gavaged group than BPH group in prostate tissue. These results suggest the beneficial effects of PE on BPH via the modulation of AR signaling pathway.

Highlights

  • Benign prostatic hyperplasia (BPH) is the most prevalent prostate disease and is one of the representative chronic diseases caused by aging in men [1]

  • The Western blotting results indicated that that DHT administration significantly increased the expression of androgen receptor (AR), prostate specific antigen (PSA), and steroid receptor coactivator 1 (SRC-1)

  • Coco-treatment with DHT and P. tenuipes extract (PE) (125, 250, or 500 μg/mL) significantly downregulated this effect treatment with DHT and PE (125, 250, or 500 μg/mL) significantly downregulated this effect (Figure (Figure 1). These results show that PE inhibits AR signaling in prostate cancer cells

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Summary

Introduction

Benign prostatic hyperplasia (BPH) is the most prevalent prostate disease and is one of the representative chronic diseases caused by aging in men [1]. DHT binds to an AR and steroid receptor coactivator 1 (SRC1); it induces the proliferation of a prostate cell [6]. -adrenergic receptor antagonists—are useful in the treatment of BPH because of their ability to relax the smooth muscle of the prostate and bladder neck, which helps urine flow. They have a limitation in that they cannot help to relieve enlargement of the prostate [10]. Previous studies showed that P. tenuipes reduced PSA mRNA expression in LNCaP cells. The studies showed that P. tenuipes inhibited the expression of angiogenesis-related factors and PSA in the cells [15]. In this study, we investigated the effect of P. tenuipes on BPH in vivo

Materials
Sample Preparation
Cell Culture
Animal Study Design
Western Blotting
Statistical
Results
Effect of PE Administration on Prostate Tissue Weight in BPH Rats
Effect of PE on Expressions of Protein in Prostate Tissue of BPH Rats
Discussion
Conclusions
Full Text
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