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Imbalance in the estrogen/androgen ratio may affect prostate fibrosis through the TGF-β/Smad signaling pathway

  • Urology - Original Paper
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Abstract

Objective

The present study aimed to investigate the effects of an imbalance in the estrogen/androgen ratio on prostate fibrosis.

Methods

Different concentrations of dihydrotestosterone (DHT) or estradiol (E2) dissolved in corn oil were injected subcutaneously into the nape of the castrated Sprague–Dawley (SD) rats over 28 consecutive days. Masson’s trichrome staining and immunohistochemical staining were performed to detect the content of collagen fibers and the expression of collagen I, fibronectin, and elastin in the rat prostate of each group, respectively. DHT + E2 at different concentrations was administered to human normal prostate stromal immortalized cells (WPMY-1 cells) for 1 week. The expression of collagen I, fibronectin, elastin, transforming growth factor-β1 (TGF-β1), Smad3, and Smad7 was detected by Western blotting (WB). Then, WPMY-1 cells treated with 10 nM DHT + 5 pM E2 were incubated with the TGF-β/Smad pathway inhibitor SD208 for 1 week, after which collagen I, fibronectin, and elastin expression was detected by WB.

Results

Compared with the uncastrated control and corn oil injection groups, the collagen fiber content and collagen I and fibronectin expression were increased and elastin expression was decreased in the castrated rat prostate with corn oil injection group (p < 0.01). Compared to castrated corn oil injection group, collagen fiber content, collagen I, and fibronectin expression were significantly decreased, and elastin expression was significantly increased in the castrated rat prostate 0.15 mg/kg DHT treatment group (p < 0.01). Following treatment with 0.15 mg/kg DHT, the content of collagen fibers, and the expression of collagen I and fibronectin were increased, and the expression of elastin was decreased in the rat prostate with increasing concentrations of E2 treatment group compared to the 0.15 mg/kg DHT group (p < 0.05, p < 0.01). Following treatment with 0.05 mg/kg E2, the collagen fiber content and the expression of collagen I and fibronectin were decreased, and the expression of elastin was increased in the rat prostate with increasing DHT concentration treatment group compared to the 0.05 mg/kg E2 group (p < 0.05, p < 0.01). Compared with the Control group, the expression of collagen I, fibronectin, TGF-β1 and Smad3 was decreased, and the expression of elastin and Smad7 was increased in WPMY-1 cells after treatment with 10 nM DHT (p < 0.01). Following treatment with 10 nM DHT, the expression of collagen I, fibronectin, TGF-β1, and Smad3 was increased, and the expression of elastin and Smad7 was decreased in WPMY-1 cells with increasing E2 concentration treatment compared to the 10 nM DHT group (p < 0.05, p < 0.01). Following treatment with 5 pM E2, the expression of collagen I, fibronectin, TGF-β1, and Smad3 was decreased, and elastin and Smad7 expression was increased with increasing DHT concentration compared to the 5 pM E2 group (p < 0.05, p < 0.01). Compared to the 10 nM DHT + 5 pM E2 group, the expressions of collagen I and fibronectin were decreased; the expression of elastin was increased in WPMY-1 cells after the supplement of TGF-β/Smad pathway inhibitor SD208 group (p < 0.05, p < 0.01).

Conclusions

An imbalance in the estrogen/androgen ratio may affect prostate fibrosis. E2 may activate the degree of prostate fibrosis. In contrast to the effect of E2, DHT may inhibit the degree of prostate fibrosis, which might involve the TGF-β/Smad signaling pathway.

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Acknowledgements

This study was supported by the grants from the National Natural Science Foundation of China (No. 81860141 and 82160149) and Guizhou Provincial Science and Technology Foundation (No. [2021]378).

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Author notes

  1. Ying Cao and Ye Tian have contributed equally to this work.

Authors and Affiliations

  1. Guizhou University School of Medicine, Guiyang, 550025, Guizhou, China

    Ying Cao

  2. Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, 550002, Guizhou, China

    Ye Tian, Heng Zhang, Guang-Heng Luo & Zhao-Lin Sun

  3. Department of Urology, Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, 200080, China

    Ye Tian & Shu-Jie Xia

Authors
  1. Ying Cao
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  2. Ye Tian
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  3. Heng Zhang
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  4. Guang-Heng Luo
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  5. Zhao-Lin Sun
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Correspondence to Shu-Jie Xia.

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Cao, Y., Tian, Y., Zhang, H. et al. Imbalance in the estrogen/androgen ratio may affect prostate fibrosis through the TGF-β/Smad signaling pathway. Int Urol Nephrol 54, 499–508 (2022). https://doi.org/10.1007/s11255-021-03079-z

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  • DOI: https://doi.org/10.1007/s11255-021-03079-z

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