Opposite effects of tamoxifen on metabolic syndrome‐induced bladder and prostate alterations: A role for GPR30/GPER?

Comeglio, Paolo; Morelli, Annamaria; Cellai, Ilaria; Vignozzi, Linda; Sarchielli, Erica; Filippi, Sandra; Maneschi, Elena; Corcetto, Francesca; Corno, C.; Gacci, Mauro; Vannelli, Gabriella Barbara; Maggi, Mario

doi:10.1002/pros.22723

Cited by 38 publications

(28 citation statements)

References 94 publications

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“…As we know, testosterone can be converted into E 2 by aromatase in the local tissue without increasing serum E 2 levels (Simpson 2003, Bell et al 2013. In order to completely exclude the effect of E 2 , in the next step we will use testosterone plus an aromatase inhibitor and analyze the expression of progesterone receptor, which was considered to be a highly estrogen-dependent gene (Comeglio et al 2014), within myocardial tissue.…”

Section: Discussionmentioning

confidence: 99%

Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction

Wang¹,

Yang²,

Sun³

et al. 2015

Journal of Endocrinology

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Testosterone can affect cardiovascular disease, but its effects on mitochondrial dynamics in the post-infarct myocardium remain unclear. To observe the effects of testosterone replacement, a rat model of castration-myocardial infarction (MI) was established by ligating the left anterior descending coronary artery 2 weeks after castration with or without testosterone treatment. Expression of mitochondrial fission and fusion proteins was detected by western blot and immunofluorescence 14 days after MI. Cardiac function, myocardial inflammatory infiltration and fibrosis, cardiomyocyte apoptosis, mitochondrial microstructure, and ATP levels were also assessed. Compared with MI rats, castrated rats showed aggravated mitochondrial and myocardial insults, including mitochondrial swelling and disordered arrangement; loss of cristae, reduced mitochondrial length; decreased ATP levels; cardiomyocyte apoptosis; and impaired cardiac function. Results of western blotting analyses indicated that castration downregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) and mitofusin 2, but upregulated dynamin-related protein 1. The results were also supported by results obtained using immunofluorescence. However, these detrimental effects were reversed by testosterone supplementation, which also elevated the upstream AMP-activated protein kinase (AMPK) activation of PGC1A. Thus, testosterone can protect mitochondria in the post-infarct myocardium, partly via the AMPK-PGC1A pathway, thereby decreasing mitochondrial dysfunction and cardiomyocyte apoptosis. The effects of testosterone were confirmed by the results of ELISA analyses.

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Section: Discussionmentioning

confidence: 99%

Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction

Wang¹,

Yang²,

Sun³

et al. 2015

Journal of Endocrinology

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“…In particular, MetS could induce or maintain an inflammatory state within the prostate that could even be exacerbated by a relative hyperoestrogenism [21] or by androgen deficiency [22,23], medical conditions often associated to MetS and in particular to increased WC [24,25].…”

Section: Discussionmentioning

confidence: 99%

“…LUTS were measured by the IPSS and categorised as storage and voiding symptoms, immediately before surgery and at 6-12 months postoperatively. The total IPSS score was categorised into 0-7, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]; storage subscore into 0-5, 6-9 and 10-15; voiding subscore into 0-6, 7-13 and 14-20 as mild, moderate and severe, respectively. For all IPSS (total, storage and voiding) the percentage of recovery of urinary symptoms after the operation (total-, storage-and voiding-Δ IPSS) was calculated using the following method: ([Preoperative IPSS -Postoperative IPSS]/Preoperative IPSS), expressed as a percentage: the full recovery of lower urinary tract function was considered as Δ = 100%.…”

Section: Methodsmentioning

confidence: 99%

Central obesity is predictive of persistent storage lower urinary tract symptoms (LUTS) after surgery for benign prostatic enlargement: results of a multicentre prospective study

et al. 2015

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Objective To evaluate the impact of components of metabolic syndrome (MetS) on urinary outcomes after surgery for severe lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE), as central obesity can be associated with the development of BPE and with the worsening of LUTS. Patients and Methods A multicentre prospective study was conducted including 378 consecutive men surgically treated for large BPE with simple open prostatectomy (OP) or transurethral resection of the prostate (TURP), between January 2012 and October 2013. LUTS were measured by the International Prostate Symptom Score (IPSS), immediately before surgery and at 6–12 months postoperatively. MetS was defined according the USA National Cholesterol Education Program‐Adult Treatment Panel III. Results The improvement of total and storage IPSS postoperatively was related to diastolic blood pressure and waist circumference (WC). A WC of >102 cm was associated with a higher risk of an incomplete recovery of both total IPSS (odds ratio [OR] 0.343, P = 0.001) and storage IPSS (OR 0.208, P < 0.001), as compared with a WC of <102 cm. The main limitations were: (i) population selected from a tertiary centre, (ii) Use exclusively of IPSS questionnaire, and (iii) No inclusion of further data. Conclusions Increased WC is associated with persistent postoperative urinary symptoms after surgical treatment of BPE. Obese men have a higher risk of persistent storage LUTS after TURP or OP.

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“…Recent data indicate that not only low testosterone but also high estradiol can favor BPH/LUTS progression. It is important to note that circulating T is actively metabolized to estrogens and part of T hormonal activity depends upon its binding to the estrogen receptors (ERs), that are present in both the prostate and bladder [26]. In addition, the enzyme P450 aromatase which converts androgens to estrogens [27] is highly expressed not only in fat tissue but also in the urogenital tract [28].…”

Section: Bph/luts and Hypogonadismmentioning

confidence: 99%

Benign Prostatic Hyperplasia: A New Metabolic Disease of the Aging Male and Its Correlation with Sexual Dysfunctions

Corona

Vignozzi

Rastrelli

et al. 2014

International Journal of Endocrinology

112

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Metabolic syndrome (MetS) is a well-recognized cluster of cardiovascular (CV) risk factors including obesity, hypertension, dyslipidemia, and hyperglycaemia, closely associated with an increased risk of forthcoming cardiovascular disease and type 2 diabetes mellitus. Emerging evidence indicates that benign prostate hyperplasia (BPH) and its related lower urinary tract symptoms (LUTS) represent other clinical conditions frequently observed in subjects with MetS. Several modifiable factors involved in MetS determinism, such as inadequate diet, lack of physical exercise, and smoking and drinking behaviours are emerging as main contributors to the development of BPH. The pathogenetic mechanisms underlying the connection between MetS and BPH have not been completely clarified. MetS and its components, hypogonadism, and prostate inflammation probably play an important role in inducing BPH/LUTS. Although historically considered as a “normal” consequence of the aging process, BPH/LUTS should now be faced proactively, as a preventable disorder of the elderly. Type of diet and level of physical activity are now considered important factors affecting prostate health in the aging male. However, whether physical exercise, weight loss, and modifications of dietary habit can really alter the natural history of BPH/LUTS remains to be determined. Further research is advisable to better clarify these points.

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Opposite effects of tamoxifen on metabolic syndrome‐induced bladder and prostate alterations: A role for GPR30/GPER?

Cited by 38 publications

References 94 publications

Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction

Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction

Central obesity is predictive of persistent storage lower urinary tract symptoms (LUTS) after surgery for benign prostatic enlargement: results of a multicentre prospective study

Benign Prostatic Hyperplasia: A New Metabolic Disease of the Aging Male and Its Correlation with Sexual Dysfunctions

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