Mechanism of action of phosphodiesterase type 5 inhibition in metabolic syndrome‐associated prostate alterations: An experimental study in the rabbit

Morelli, Annamaria; Comeglio, Paolo; Filippi, Sandra; Sarchielli, Erica; Vignozzi, Linda; Maneschi, Elena; Cellai, Ilaria; Gacci, Mauro; Lenzi, Andrea; Vannelli, Gabriella Barbara; Maggi, Mario

doi:10.1002/pros.22584

Cited by 77 publications

(98 citation statements)

References 35 publications

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“…1A). MetS rabbits were characterized by a sex steroid imbalance, including reduced testosterone and elevated estradiol (E 2 ) plasma levels, as previously published (Filippi et al 2009, Morelli et al 2012a,b, Vignozzi et al 2012. Interestingly, DT (testosterone at 12 weeksKtestosterone at baseline) negatively (rZK0 .…”

Section: Discussionmentioning

confidence: 88%

“…VAT was harvested from the different experimental groups and appropriately processed for the subsequent analyses and preadipocyte isolation. Biochemical and hormonal serum analyses were performed as described previously (Filippi et al 2009, Morelli et al 2012a,b, Vignozzi et al 2012. Animal handling complied with the Institutional Animal Care and Use Committee of the University of Florence, Florence, Italy, in accordance with the Italian Ministerial Law # 116/92.…”

Section: Mets Rabbit Modelmentioning

confidence: 99%

“…injected 1 h before killing, as described previously (Morelli et al 2012a,b, Vignozzi et al 2012. VAT samples were rapidly removed and fixed in 4% neutral-buffered formalin, dehydrated, and embedded in paraffin.…”

Section: Hypoxia Detection and Immunohistochemistrymentioning

confidence: 99%

“…Quantitative RT-PCR (qRT-PCR) was performed using SsoFastTM EvaGreen Supermix (Bio-Rad Laboratories) as previously reported (Morelli et al 2012a,b). Specific primers for all the target genes were either previously reported (Filippi et al 2009, Morelli et al 2012a,b, Vignozzi et al 2012 or reported in Table 1. The expression of 18S ribosomal RNA subunit, quantified with a predeveloped assay (Applied Biosystems), was chosen as reference gene and used for relative quantitation of the target genes.…”

Section: Rna Extraction and Quantitative Rt-pcr Analysismentioning

confidence: 99%

“…Such a model essentially recapitulates the human MetS phenotype (hypertension, hyperglycemia, dyslipidemia, visceral fat accumulation, and reduced glucose tolerance), including a condition of hypogonadotropic hypogonadism (Filippi et al 2009). Interestingly, testosterone dosing in MetS rabbits not only drastically prevented the HFD-induced VAT expansion but also reduced fasting glucose and improved glucose tolerance (Filippi et al 2009, Vignozzi et al 2011, Morelli et al 2012a. Using this HFD-induced MetS model, the aim of this study is to investigate the role played by testosterone in adipose tissue dysfunction in this experimental MetS condition.…”

Section: Introductionmentioning

confidence: 99%

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Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements

Maneschi¹,

Morelli²,

Filippi³

et al. 2012

Journal of Endocrinology

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We recently demonstrated that testosterone dosing ameliorated the metabolic profile and reduced visceral adipose tissue (VAT) in a high-fat diet (HFD)-induced rabbit model of metabolic syndrome (MetS). We studied the effects of HFD and in vivo testosterone dosing on VAT function and the adipogenic capacity of rabbit preadipocytes isolated from VAT of regular diet (RD), HFD, and testosterone-treated HFD rabbits. VAT was studied by immunohistochemistry, western blot, and RT-PCR. Isolated rPADs were exposed to adipocyte differentiating mixture (DIM) to evaluate adipogenic potential. Adipocyte size was significantly increased in HFD VAT compared with RD, indicating adipocyte dysfunction, which was normalized by testosterone dosing. Accordingly, perilipin, an anti-lipolytic protein, was significantly increased in HFD VAT, when compared with other groups. HFD VAT was hypoxic, while testosterone dosing normalized VAT oxygenation. In VAT, androgen receptor expression was positively associated with mRNA expression of GLUT4 (SLC2A4) (insulin-regulated glucose transporter) and STAMP2 (STEAP4) (androgen-dependent gene required for insulin signaling). In testosterone-treated HFD VAT, STAMP2 mRNA was significantly increased when compared with the other groups. Moreover, GLUT4 membrane translocation was significantly reduced in HFD VAT, compared with RD, and increased by testosterone. In DIM-exposed preadipocytes from HFD, triglyceride accumulation, adipocyte-specific genes, insulin-stimulated triglyceride synthesis, glucose uptake, and GLUT4 membrane translocation were reduced compared with preadipocytes from RD and normalized by in vivo testosterone dosing. In conclusion, testosterone dosing in a MetS animal model positively affects VAT functions. This could reflect the ability of testosterone in restoring insulin sensitivity in VAT, thus counteracting metabolic alterations.

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Section: Discussionmentioning

confidence: 88%

Section: Mets Rabbit Modelmentioning

confidence: 99%

Section: Hypoxia Detection and Immunohistochemistrymentioning

confidence: 99%

Section: Rna Extraction and Quantitative Rt-pcr Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements

Maneschi¹,

Morelli²,

Filippi³

et al. 2012

Journal of Endocrinology

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Comparison of cernitin pollen extract vs tadalafil therapy for refractory chronic prostatitis/chronic pelvic pain syndrome: A randomized, prospective study

Matsukawa

Naito

Funahashi

et al. 2020

Neurourology and Urodynamics

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Aims To compare the efficacy of cernitin pollen extract (cernitin) or tadalafil for treating persistent chronic pelvic pain despite α1‐blocker monotherapy in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and lower urinary tract symptoms (LUTS). Methods A total of 100 patients with refractory CP/CPPS despite ongoing α1‐blocker monotherapy were randomized to receive add‐on therapy with either cernitin (4 capsules/day) or tadalafil (5 mg/d) for 12 weeks. At week 12, changes from baseline in the patients’ CP/CPPS, LUTS, and voiding function, as assessed using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH‐CPSI), the International Prostate Symptom Score (IPSS), and uroflowmetry, respectively, were compared between the groups. Results The final analysis included 42 and 45 patients in the cernitin and tadalafil groups, respectively. Although the NIH‐CPSI total, NIH‐CPSI pain sub‐score, and NIH‐CPSI quality of life sub‐score significantly improved in both groups, the cernitin (vs tadalafil) group showed significantly greater improvements in the NIH‐CPSI total score (−6.8 vs −4.6; P = .02) and NIH‐CPSI pain sub‐score (−4.1 vs −1.5; P < .001). Half (50%) of the patients in the cernitin group showed a reduction greater than 50% in their NIH‐CPSI pain sub‐score; in the tadalafil group, only four patients (8.9%) showed ≥50% improvement (P < .001). In contrast, the improvement in LUTS was significantly superior in the tadalafil group. Conclusion Both cernitin and tadalafil significantly ameliorated chronic pelvic pain in patients with refractory CP/CPPS. The add‐on of cernitin was more effective than tadalafil for pelvic pain and discomfort.

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Mechanisms of synergism between antagonists of growth hormone‐releasing hormone and antagonists of luteinizing hormone‐releasing hormone in shrinking experimental benign prostatic hyperplasia

et al. 2012

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Mechanism of action of phosphodiesterase type 5 inhibition in metabolic syndrome‐associated prostate alterations: An experimental study in the rabbit

Abstract: Our data provide the experimental evidences to support the multiple potentiality of PDE5 inhibitors as a useful therapeutic tool in LUTS.

Cited by 77 publications

References 35 publications

Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements

Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements

Comparison of cernitin pollen extract vs tadalafil therapy for refractory chronic prostatitis/chronic pelvic pain syndrome: A randomized, prospective study

Mechanisms of synergism between antagonists of growth hormone‐releasing hormone and antagonists of luteinizing hormone‐releasing hormone in shrinking experimental benign prostatic hyperplasia

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