Castration Impairs Erectile Organ Structure and Function by Inhibiting Autophagy and Promoting Apoptosis of Corpus Cavernosum Smooth Muscle Cells in Rats

Overview

Journal Int Urol Nephrol

Publisher Springer

Specialty Nephrology

Date 2015 May 23

PMID 25997594

Citations 13

Authors

Xian-Jin Wang

Tian-Yuan Xu

Lei-Lei Xia

Shan Zhong

Xiao-Hua Zhang

Zhao-Wei Zhu

Dong-Rui Chen

Yue Liu

Yong Fan

Chen Xu

Min-Guang Zhang

Zhou-jun Shen

Affiliations

Soon will be listed here.

Abstract

Objective: The aim of this study was to determine the changes and underlying mechanisms of erectile organ structure and function in castrated rats. In addition, the regulatory effects of an androgen on autophagy and apoptosis in corpus cavernosum smooth muscle cells (CCSMCs), especially the regulatory effect of androgen on the BECN 1-Bcl-2 interaction, were investigated.

Methods: Male Sprague-Dawley rats were divided into three groups (30/group): control group, castration group, and castration with testosterone supplementation group. The erectile function was examined both in vivo and in vitro, by electric stimulation of the cavernous nerve and corpus cavernosum strip bath test, respectively. Transmission electron microscopy, TUNEL assay, Masson's trichrome staining, immunohistochemistry, and western blotting were performed to determine the levels of autophagy and apoptosis, and the structural changes in corpus cavernosum.

Results: Compared with control group, the castration group showed (1) lower erectile function: lower intracavernosal pressure/mean arterial pressure ratio, lower systolic and diastolic capability of corporal strips, and reduced expressions of eNOS and nNOS; (2) greater fibrosis: decreased smooth muscle/collagen ratio, lower expression of α-SMA, and higher expression of TGF-β1; (3) inhibited autophagy: decreased autophagosomes, lower expressions of BECN1 and LC3-II; and (4) enhanced apoptosis: higher apoptotic index and decreased Bcl-2/Bax ratio. Testosterone supplementation partially improved the effects of castration.

Conclusions: Castration attenuates erectile function and induces corporeal fibrosis by inhibiting autophagy and promoting apoptosis of CCSMCs in rats. Therefore, our study highlights the important role of androgens in maintaining the integrity of the structure and function of corpus cavernosum in rats through counter-regulation of autophagy and apoptosis, mainly by regulating BECN 1-Bcl-2 interaction.

Citing Articles

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Hyperprolactinemia and male sexual function: focus on erectile dysfunction and sexual desire.

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Long-term administration of resveratrol and MitoQ stimulates cavernosum antioxidant gene expression in a mouse castration model of erectile dysfunction.

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Role of Glucose-Lowering Medications in Erectile Dysfunction.

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