Prostate volume in male patients with spinal cord injury: a question of nerves?

Pannek, Jürgen; Bartel, Peter; Göcking, K; Frotzler, Angela

doi:10.1111/bju.12027

Cited by 11 publications

(4 citation statements)

References 21 publications

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“…We observed a reduction in prostate mass in rodents receiving SCI, which is similar to that which occurs in men after SCI 49 and may be related to the high prevalence of hypogonadism within this population. 40 In an attempt to limit androgeninduced prostate enlargement, we administered TE in a low-dose (that has previously been reported to restore sex-organ weight and normal sexual and nonsexual behavior in chemically castrated rats).…”

Section: Mechanisms Of Testosterone Actionsupporting

confidence: 73%

Testosterone Dose Dependently Prevents Bone and Muscle Loss in Rodents after Spinal Cord Injury

Yarrow

Conover²,

Beggs

et al. 2014

Journal of Neurotrauma

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Androgen administration protects against musculoskeletal deficits in models of sex-steroid deficiency and injury/disuse. It remains unknown, however, whether testosterone prevents bone loss accompanying spinal cord injury (SCI), a condition that results in a near universal occurrence of osteoporosis. Our primary purpose was to determine whether testosterone-enanthate (TE) attenuates hindlimb bone loss in a rodent moderate/severe contusion SCI model. Forty (n=10/group), 14 week old male Sprague-Dawley rats were randomized to receive: (1) Sham surgery (T9 laminectomy), (2) moderate/severe (250 kdyne) SCI, (3) SCI+Low-dose TE (2.0 mg/week), or (4) SCI+High-dose TE (7.0 mg/week). Twenty-one days post-injury, SCI animals exhibited a 77-85% reduction in hindlimb cancellous bone volume at the distal femur (measured via μCT) and proximal tibia (measured via histomorphometry), characterized by a >70% reduction in trabecular number, 13-27% reduction in trabecular thickness, and increased trabecular separation. A 57% reduction in cancellous volumetric bone mineral density (vBMD) at the distal femur and a 20% reduction in vBMD at the femoral neck were also observed. TE dose dependently prevented hindlimb bone loss after SCI, with high-dose TE fully preserving cancellous bone structural characteristics and vBMD at all skeletal sites examined. Animals receiving SCI also exhibited a 35% reduction in hindlimb weight bearing (triceps surae) muscle mass and a 22% reduction in sublesional non-weight bearing (levator ani/bulbocavernosus [LABC]) muscle mass, and reduced prostate mass. Both TE doses fully preserved LABC mass, while only high-dose TE ameliorated hindlimb muscle losses. TE also dose dependently increased prostate mass. Our findings provide the first evidence indicating that high-dose TE fully prevents hindlimb cancellous bone loss and concomitantly ameliorates muscle loss after SCI, while low-dose TE produces much less profound musculoskeletal benefit. Testosterone-induced prostate enlargement, however, represents a potential barrier to the clinical implementation of high-dose TE as a means of preserving musculoskeletal tissue after SCI.

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Section: Mechanisms Of Testosterone Actionsupporting

confidence: 73%

Testosterone Dose Dependently Prevents Bone and Muscle Loss in Rodents after Spinal Cord Injury

Yarrow

Conover²,

Beggs

et al. 2014

Journal of Neurotrauma

View full text Add to dashboard Cite

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“…Studies in rats have shown that denervation of the prostate leads to almost complete loss of epithelium (14), indicating a strong trophic effect of nerves on normal prostate epithelium. Similarly, men with complete spinal cord injury had significantly smaller prostates than controls(15). Studies by Magnon et al(16) have shown that chemical or surgical ablation of nerves inhibits tumorigenesis and metastasis in both xenograft and transgenic mouse models of PCa, unequivocally establishing that nerve-PCa cell interactions play a significant role in PCa initiation and progression but the molecular basis of these interactions is still unclear.…”

Section: Introductionmentioning

confidence: 99%

RET Signaling in Prostate Cancer

Ban

Feng

Shao

et al. 2017

Clinical Cancer Research

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Purpose Large diameter perineural prostate cancer is associated with poor outcomes. GDNF, with its co-receptor GFRα1, binds RET and activates downstream pro-oncogenic signaling. Since both GDNF and GFRα1 are secreted by nerves, we examined the role of RET signaling in prostate cancer. Experimental Design Expression of RET, GDNF and/or GFRα1 was assessed. The impact of RET signaling on proliferation, invasion and soft agar colony formation, perineural invasion and growth in vivo was determined. Cellular signaling downstream of RET was examined by Western blotting. Results RET is expressed in all prostate cancer cell lines. GFRα1 is only expressed in 22Rv1 cells, which is the only line that responds to exogenous GDNF. In contrast, all cell lines respond to GDNF plus GFRα1. Conditioned medium from dorsal root ganglia contains secreted GFRα1 and promotes transformation related phenotypes, which can be blocked by anti-GFRα1 antibody. Perineural invasion in the dorsal root ganglion assay is inhibited by anti-GFRα antibody and RET knockdown. In vivo, knockdown of RET inhibits tumor growth. RET signaling activates ERK or AKT signaling depending on context, but phosphorylation of p70S6 kinase is markedly increased in all cases. Knockdown of p70S6 kinase markedly decreases RET induced transformed phenotypes. Finally, RET is expressed in 18% of adenocarcinomas and all three small cell carcinomas examined. Conclusions RET promotes transformation associated phenotypes, including perineural invasion in prostate cancer via activation of p70S6 kinase. GFRα1, which is secreted by nerves, is a limiting factor for RET signaling, creating a perineural niche where RET signaling can occur.

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“…Brasso et al reported that SP concentrations of KLK3 were significantly lower in SCI patients with lesions below T7 compared with patients with lesions at or above this level (52). Studies have shown that the prostate gland is smaller in men with SCI compared with healthy, noninjured men, and that this effect may be because of a prolonged central (rather than peripheral) desinnervation of the prostate gland (55). However, further pathophysiological studies of the prostate gland are necessary to investigate how a neurological trauma influences glandular function.…”

Section: Qualitative Map Of the Human Seminal Plasma Proteome-mentioning

confidence: 99%

Towards Understanding Male Infertility After Spinal Cord Injury Using Quantitative Proteomics

Silva

Meng

Helm

et al. 2016

Molecular & Cellular Proteomics

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The study of male infertility after spinal cord injury (SCI) has enhanced the understanding of seminal plasma (SP) as an important regulator of spermatozoa function. However, the most important factors leading to the diminished sperm motility and viability observed in semen of men with SCI remained unknown. Thus, to explore SP related molecular mechanisms underlying infertility after SCI, we used mass spectrometry-based quantitative proteomics to compare SP retrieved from SCI patients to normal controls. As a result, we present an in-depth characterization of the human SP proteome, identifying ϳ2,800 individual proteins, and describe, in detail, the differential proteome observed in SCI. Our analysis demonstrates that a hyper-activation of the immune system may influence some seminal processes, which likely are not triggered by microbial infection. Moreover, we show evidence of an important prostate gland functional failure, i.e. diminished abundance of metabolic enzymes related to ATP turnover and those secreted via prostasomes. Further we identify the main outcome related to this fact and that it is intrinsically linked to the low sperm motility in SCI. Together, our data highlights the molecular pathways hindering fertility in SCI and shed new light on other causes of male infertility. Molecular & Cellular Proteomics 15: 10.1074/mcp.M115.052175, 1424-1434, 2016.For many years, seminal plasma (SP) 1 , the liquid component of semen, was believed to have a single and simple physiological significance as the carrier of spermatozoa through both male and female reproductive tracts. It was around 50 years ago when the compositional complexity of this fluid started to be investigated, demonstrating that SP not only aids in cellular transport but also provides energy and metabolic support to the transiting spermatozoa (1, 2). Today, growing evidence indicates that SP plays a role far beyond what was once envisioned, including acting as an essential regulator of spermatozoa function contributing to (enabling/ hindering) the cellular ability of fertilization (3). Composed of secretions derived from the testis, epididymis and male accessory glands (prostate, seminal vesicles and bulbourethral glands), SP is a mixture of sugars, inorganic ions, organic salts, (phospho)lipids and proteins (4). Such a heterogeneous composition emphasizes the complex biochemical cascades triggered within SP during, and immediately after, ejaculation and defines the beneficial and/or detrimental nature of SP in the overall reproductive process (5). From a clinical point of view, studies have confirmed the participation of SP in the etiology of male infertility. By studying semen of men with spinal cord injury (SCI), who become infertile after a traumatic injury and often present with an unusual seminal profile characterized by normal sperm concentration but extremely impaired sperm motility and viability, Brackett et al. demonstrated how SP can impair sperm function leading to infertility (6). Specifically, the authors mixed SP obtained from ...

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Prostate volume in male patients with spinal cord injury: a question of nerves?

Cited by 11 publications

References 21 publications

Testosterone Dose Dependently Prevents Bone and Muscle Loss in Rodents after Spinal Cord Injury

Testosterone Dose Dependently Prevents Bone and Muscle Loss in Rodents after Spinal Cord Injury

RET Signaling in Prostate Cancer

Towards Understanding Male Infertility After Spinal Cord Injury Using Quantitative Proteomics

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