Castration impairs erectile organ structure and function by inhibiting autophagy and promoting apoptosis of corpus cavernosum smooth muscle cells in rats

Wang, Xianjin; Xu, Tianmin; Xia, Leilei; Zhong, Shan; Zhang, Xiaohua; Zhu, Zhaowei; Chen, Dong-Rui; Liu, Yue; Fan, Yong; Chen, Xu; Zhang, Minguang; Zhang, Shen

doi:10.1007/s11255-015-1011-3

Cited by 39 publications

(29 citation statements)

References 54 publications

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“…Castration of rodent animal models results in reduced erectile function, as evidence by lowered development of intracorporal pressure following cavernous nerve stimulation [25–29]. Several investigators have proposed that change in penile architecture is the main mediator of the effects of androgen deprivation which produces penile tissue atrophy concomitant with alterations in dorsal nerve structure, endothelial morphology, reduction in trabecular smooth muscle content, increased deposition of extracellular matrix and accumulation of fat-containing cells (adipocytes) in the sub-tunical region of the corpus cavernosum [30–36]. The androgen-dependent loss of erectile response is restored by androgen administration where there is some evidence that the mechanism may involve differentiation of progenitor cells into smooth muscle cells and inhibition of their differentiation into adipocytes [28, 29, 35,37–38].…”

Section: Role Of Testosterone In Cellular Physiology: John Mulhall Kmentioning

confidence: 99%

“…It has been shown that castration results in erectile dysfunction [31, 35] and reversibly alters corpora cavernosal architecture. Trabecular smooth muscle content decreases [29, 36] while connective tissue abundance increases [31, 36]. In addition, fat-containing cells accumulate in the corpora cavernosa [31], resulting from androgen deprivation effects on progenitor stromal cells causing them to differentiate into an adipogenic lineage [31].…”

Section: Testosterone Effects On Penile Development and Adult Penile mentioning

confidence: 99%

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Translational Perspective on the Role of Testosterone in Sexual Function and Dysfunction

Podlasek

Mulhall

Davies

et al. 2016

The Journal of Sexual Medicine

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Introduction The biological importance of testosterone is generally accepted by the medical community, however controversy focuses on its relevance to sexual function and the sexual response, and our understanding of the extent of its role in this area is evolving. Aim This article aims to provide scientific evidence examining the role of testosterone at the cellular and molecular levels as it pertains to normal erectile physiology and the development of erectile dysfunction, and to assist in guiding successful therapeutic interventions for androgen-dependent sexual dysfunction. Methods In this White Paper, the Basic Science Committee of the Sexual Medicine Society of North America assessed the current basic science literature examining the role of testosterone in sexual function and dysfunction. Results Testosterone plays an important role in sexual function via multiple processes: physiological (stimulates activity of NOS), developmental (establish and maintain the structural and functional integrity of the penis), neural (development, maintenance, function and plasticity of the cavernous nerve and pelvic ganglia), therapeutically for dysfunctional regulation (beneficial effect on aging, diabetes and prostatectomy), and PDE5i (testosterone supplement to counteract PDE5i resistance). Conclusions Despite controversies surrounding testosterone with regard to sexual function, basic science studies provide incontrovertible evidence for a significant role of testosterone in sexual function and suggest that properly administered testosterone therapy is potentially advantageous for treating male sexual dysfunction.

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Section: Role Of Testosterone In Cellular Physiology: John Mulhall Kmentioning

confidence: 99%

Section: Testosterone Effects On Penile Development and Adult Penile mentioning

confidence: 99%

Translational Perspective on the Role of Testosterone in Sexual Function and Dysfunction

Podlasek

Mulhall

Davies

et al. 2016

The Journal of Sexual Medicine

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show abstract

“…Autophagy has also been implicated in other animal models of ED. Wang et al showed that castration leads to ED and induced CC fibrosis by suppressing autophagy and enhancing apoptosis in rats CSMCs (Wang et al, 2015). Li et al demonstrated that autophagy is inhibited in a hyperlipidemia rat ED model, which was considered to be part of the pathogenic mechanism (Li et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Autophagy also plays a significant role in age-related ED. Wang et al showed that castration leads to ED and induced CC fibrosis by suppressing autophagy and enhancing apoptosis in rats CSMCs (Wang et al, 2015). Moreover, autophagosome number is remarkably reduced in the CSMCs of aging rats.…”

Section: Figurementioning

confidence: 99%

Human tissue kallikrein 1 ameliorates erectile function via modulation of macroautophagy in aged transgenic rats

et al. 2018

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Previously, we have demonstrated that human tissue kallikrein 1 (hKLK1) improves age-related erectile dysfunction (ED). Autophagy has been implicated in age-related diseases, including ED. However, the molecular mechanisms underlying hKLK1-mediated amelioration of age-related ED via regulation of autophagy remains unknown. To explore the potential mechanism, male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring human KLK1 (TGR) were bred till 4 or 18 months of age and divided into three groups: young WTR (yWTR) as the control group, aged WTR (aWTR) group, and aged TGR (aTGR) group. The erectile function of each rat was evaluated using cavernous nerve electrostimulation. The ratio of intracavernous pressure/mean arterial pressure (ICP/MAP) and total ICP were also measured. Western blotting, immunohistochemistry, and transmission electron microscopy were performed to detect the levels of autophagy. The expression levels of related signaling pathways were determined by western blotting and immunohistochemistry. We found that hKLK1 improved the impaired erectile function of aged rats. Compared to the yWTR and aTGR groups, the aWTR group showed reduced smooth muscle/collagen ratio, fewer autophagosomes, and lower expression of Beclin 1 and LC3-II, which indicate impaired smooth muscle function and low level of autophagy in the smooth muscle cells. Moreover, the PI3K/Akt/mTOR signaling pathway, which is considered to be a negative regulator of autophagy, was upregulated in the aWTR group. hKLK1 may partially restore erectile function in aged transgenic rats by upregulating protective autophagy via the PI3K/Akt/mTOR pathway. These observations indicate that hKLK1 is a potential gene therapy candidate for age-related ED.

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“…Administration of PDE5-Is was shown to effectively prevent PL shortening (Berookhim et al, 2014;Montorsi et al, 2014), while preserved postoperative PL was shown to correlate well with the maintenance of erectile function after nerve-sparing RP (Briganti et al, 2007;Engel et al, 2011). One study utilizing a castrated animal model showed greater fibrosis and enhanced apoptosis of the penis tissues (Wang et al, 2015), while another reported internal pudendal artery dysfunction (Alves-Lopes et al, 2017). Despite varying widely, erectile function among our study population was generally poor.…”

Section: Discussionmentioning

confidence: 99%

Changes in penile length after radical prostatectomy: effect of neoadjuvant androgen deprivation therapy

et al. 2018

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Although reports have shown evidence for penile length (PL) shortening after radical prostatectomy (RP), the association between neoadjuvant androgen deprivation therapy (NADT) and PL after RP has yet to be determined. This study evaluates chronological changes in PL after NADT and RP. Stretched PLs (SPLs) of 143 patients, 41 of whom had undergone NADT, were measured before, 10 days after, and 1, 3, 6, 9, 12, 18, and 24 months after RP. Chronological erectile function and testosterone levels were then evaluated. SPL was shortest 10 days after RP in both the NADT (-) and NADT (+) groups and gradually recovered in length thereafter. SPL in the NADT (-) group was significantly longer than that in the NADT (+) group before RP. However, no significant differences in SPLs were found between both groups 6 months after RP. Although all subjects in the NADT (+) group had testosterone levels of <50 ng/dL before RP, such levels increased after RP. Before RP, the NADT (-) group was found to have significantly better erectile function than the NADT (+) group. However, differences in erectile function between the NADT (-) and NADT (+) groups after RP were not significant. This report is the first to show that among patients with prostate cancer, those who underwent NADT had greater PL recovery after RP than those who did not. Data regarding PL recovery after NADT and RP obtained in this study could be useful for patients with prostate cancer who plan to undergo such procedures.

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Castration impairs erectile organ structure and function by inhibiting autophagy and promoting apoptosis of corpus cavernosum smooth muscle cells in rats

Cited by 39 publications

References 54 publications

Translational Perspective on the Role of Testosterone in Sexual Function and Dysfunction

Translational Perspective on the Role of Testosterone in Sexual Function and Dysfunction

Human tissue kallikrein 1 ameliorates erectile function via modulation of macroautophagy in aged transgenic rats

Changes in penile length after radical prostatectomy: effect of neoadjuvant androgen deprivation therapy

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