Endocrine Abstracts (2011) 26 P349

Beneficial effects of testosterone supplementation on prostatitis-like alterations in an animal model of metabolic syndrome

A Morelli, S Filippi, L Vignozzi, P Comeglio, E Sarchielli, E Maneschi, I Cellai, G B Vannelli & M Maggi

University of Florence, Florence, Italy.

Introduction: Several studies suggested a direct relationship between metabolic syndrome (MetS) and increased risk of benign prostatic hyperplasia (BPH). An inflammatory component, mainly mediated by IL-8, has been proposed as the primary link between MetS and BPH pathogenesis. MetS, is often associated with testosterone (T) deficiency and an imbalance between the androgen and estrogen ratio characterizes BPH patients.

Methods: We investigated the effects of in vivo T supplementation on MetS-related prostate alterations, using a previously characterized high fat diet (HFD)-induced rabbit model of MetS. Untreated HFD rabbits and rabbits fed a standard diet (control) were used for comparison. The effect of the not-aromatizable T metabolite, dihydrotestosterone (DHT), was studied in human prostatic stromal cells (hBPH).

Results: HFD rabbits developed all features of Mets, including dislipidemia, hyperglicemia, glucose intolerance, hypertension, visceral obesity and hypogonadism. In addition, HFD rabbits showed prostatitis-like symptoms, such as prostate fibrosis, hypoxia, lymphocyte infiltration and formation of corpora amylacea, a typical sign of inflamed prostate. Accordingly, mRNA expression of several inflammatory (TNFα, IL8, IL6, IL1β, TLR2, TLR4), T-lymphocyte (CD4, CD8), and fibrosis/myofibroblast activation (TGFβ, MMP9, RhoA, ROCK1) markers was significantly increased in prostate samples from HFD-rabbits, when compared to control rabbits. T supplementation prevented not only some MetS features (glucose intolerance and visceral fat accumulation) but also all HFD-induced prostate alterations. Moreover, features of liver steatosis and inflammation, observed in HFD rabbits, were not affected by T treatment, indicating a tissue-specific effect of T on prostate. hBPH cells exposed to TNFα stimulus showed a significantly increased secretion of IL8 and other cytokines/chemokines (IL6, MCP1, eotaxin, IP10). Preincubating cells with 30 nM DHT prevented TNFα-induced cytokine secretion.

Conclusion: Overall, our results suggest that anti-inflammatory properties of androgens could counteract the development of MetS-related prostatitis-like alterations.

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