Effects of Supraphysiological Testosterone Treatment and Orchiectomy on Ischemia/Reperfusion-Induced Bladder Dysfunction in Male Rabbits

Authors

  • Shu-Mien Chuang PhD,

    1. Yuh-Ing Junior College of Health Care and Management, Kaohsiung, Taiwan
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  • Keh-Min Liu PhD,

    1. Department of Anatomy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Yung-Chin Lee MD, PhD,

    1. Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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  • Rong-Jyh Lin PhD,

    1. Department of Parasitology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Chao-Yuan Chang MS,

    1. Department of Anatomy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Wen-Jen Wu MD, PhD,

    1. Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
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  • Wei-Chiao Chang PhD,

    1. Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taiwan
    2. Department of Pharmacy, Taipei Medical University – Wanfang Hospital, Taipei, Taiwan
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  • Robert M. Levin PhD,

    1. Albany College of Pharmacy, Albany, NY, USA
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  • Yung-Shun Juan MD, PhD

    Corresponding author
    1. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
    2. Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
    • Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • The first two authors contributed equally to this manuscript.

Corresponding Author: Yung-Shun Juan MD, PhD, Department of Urology, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road Sanmin District, Kaohsiung City 807, Taiwan. Tel: 886-7-3121101; Fax: 886-7-3506269; E-mail: ruanusuro@yahoo.com.tw

Abstract

Introduction

The roles of testosterone and orchiectomy on male bladder subjected to ischemic/reperfusion (I/R) injuries received little attention. To fill this gap, the present study intended to examine testosterone and orchiectomy effects on male rabbits subjected to I/R damages.

Aim

To elucidate the effects of testosterone and orchiectomy on contractile response, bladder morphology, interstitial fibrosis, and oxidative stress in male rabbit bladder subjected to I/R surgery.

Methods

Male New Zealand rabbits were distributed into five groups as follows: Group 1 received sham surgical procedure. In group 2, I/R surgery was performed. In group 3, testosterone (100 μg/kg/day) was intramuscularly injected prior to I/R surgery. In group 4, orchiectomy was performed prior to I/R surgery. In group 5, orchiectomy was performed with subsequent testosterone administration, followed by I/R surgery. All the rabbits were euthanized 7 days after I/R. Comparative studies were analyzed to elucidate the effects of testosterone and orchiectomy on bladder dysfunction subjected to I/R injuries.

Main Outcome Measures

Bladder contractile function was evaluated. Masson's trichrome staining and immunohistochemical studies were performed to evaluate bladder morphology and intramural nerve terminals. Western blotting was examined to investigate the expressions of fibrosis and oxidative stress markers.

Results

I/R surgery significantly decreased bladder contractility in response to various stimulations with and without testosterone treatment. I/R damages decreased bladder nerve density with and without testosterone. The expressions of fibrosis and oxidative stress-related proteins were increased by I/R injuries with or without testosterone treatment. Testosterone depletion significantly decreased the expressions of transforming growth factor-β and fibronectin expressions after I/R injury. Supraphysiological testosterone treatment after orchiectomy greatly increased the expressions of these fibrosis proteins; however, orchiectomy alone ameliorated I/R injuries.

Conclusions

Testosterone treatment or orchiectomy affected I/R-induced bladder damages in male rabbits. Orchiectomy decreased the level of fibrosis and oxidative stress markers and increased neurofilament densities. Supraphysiological exogenous testosterone administration after orchiectomy further exacerbated such detrimental effects of I/R.

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