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Alterations in the balance of sex hormones may affect rat prostatic inflammation and fibrosis, and osteopontin might be involved in this process

  • Nephrology - Original Paper
  • Published:
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Abstract

Objective

This study aimed to investigate the effects of sex hormone imbalance on rat prostatic inflammation and fibrosis and identify the key molecules involved.

Methods

Castrated Sprague–Dawley (SD) rats were treated with a constant dose of oestradiol (E2) and different doses of dihydrotestosterone (DHT) to achieve different oestrogen/androgen ratios. After 8 weeks, serum E2 and DHT concentrations, relative seminal vesicle weights, histopathological changes and inflammation were measured, collagen fiber content and oestrogen receptor (ER) and androgen receptor (AR) expression were detected, mRNA sequencing and bioinformatics analysis were performed to identify differentially expressed genes (DEGs).

Results

The severity of inflammation in the rat dorsolateral prostate (DLP) was higher, collagen fibre content and ER expression in the rat DLP and prostatic urethra were increased and AR expression in the rat DLP was decreased in the 1:1 E2/DHT-treated group than that in the 1:10 E2/DHT-treated group. RNA-seq analysis identified 487 DEGs, and striking increases in the expression of mRNAs encoding collagen, collagen synthesis and degradation enzymes, growth factors and binding proteins, cytokines and chemokines, and cell-surface molecules were confirmed in the 1:1 E2/DHT-treated group compared to the 1:10 E2/DHT-treated group. mRNA expression of secreted phosphoprotein 1 (Spp1) and protein expression of osteopontin (OPN, encoded by Spp1) were increased in the 1:1 E2/DHT-treated group compared to the 1:10 E2/DHT-treated group, and Spp1 expression correlated positively with Mmp7, Cxcl6 and Igfn1 expression.

Conclusions

The imbalance in the oestrogen/androgen ratio may affect rat prostatic inflammation and fibrosis, and OPN might be involved in this process.

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Data availability

All data included in this study are available upon request by contact with the corresponding author.

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Acknowledgements

The study is supported financially by a grant from the National Natural Science Foundation of China (No. 81860141 and 82160149), Guizhou Provincial Science and Technology Foundation (No. [2021]378 and No.gzwkj2013-1-105, Guizhou University introduces talents Foundation (No.[2021]8).

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Author notes

  1. Ying Cao and Heng Zhang contributed equally to this work.

Authors and Affiliations

  1. Guizhou University Medical College, Guiyang, 550025, China

    Ying Cao, Mu-Xia Luo & Lei Tang

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

    Heng Zhang, Xiao-Hu Tang, Ye Tian, Guang-Heng Luo, Yan-Dong Wang, Zhen Wang & Lin-yue An

  3. Department of Pathology, Guizhou Provincial People’s Hospital, Guiyang, 550002, China

    Gui-Lan Tu

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  1. Ying Cao
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Cao, Y., Zhang, H., Tang, XH. et al. Alterations in the balance of sex hormones may affect rat prostatic inflammation and fibrosis, and osteopontin might be involved in this process. Int Urol Nephrol 55, 2355–2365 (2023). https://doi.org/10.1007/s11255-023-03544-x

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