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Fat boosts, while androgen receptor activation counteracts, BPH‐associated prostate inflammation
Author(s) -
Vignozzi Linda,
Gacci Mauro,
Cellai Ilaria,
Santi Raffaella,
Corona Giovanni,
Morelli Annamaria,
Rastrelli Giulia,
Comeglio Paolo,
Sebastanelli Arcangelo,
Maneschi Elena,
Nesi Gabriella,
De Nunzio Cosimo,
Tubaro Andrea,
Mannucci Edoardo,
Carini Marco,
Maggi Mario
Publication year - 2013
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22623
Subject(s) - medicine , endocrinology , inflammation , prostate , metabolic syndrome , dyslipidemia , bicalutamide , testosterone (patch) , hyperplasia , dihydrotestosterone , androgen receptor , prostate diseases , prostate cancer , androgen , diabetes mellitus , hormone , cancer
BACKGROUND Metabolic syndrome (MetS) and benign prostate hyperplasia (BPH) are often comorbid. Chronic inflammation, a determinant pathogenic factor for BPH, is a putative link between the two conditions. METHODS In a multi‐center cohort of BPH patients (n = 244) who underwent prostatectomy, we evaluated whether MetS is associated with prostatic inflammation in BPH specimens. In addition, we investigated the in vitro inflammatory effects of metabolic insults on human prostatic myofibroblastic cells (hBPH). RESULTS Inflammatory infiltrates score (IS) in prostatectomy specimens showed a step‐wise association with the number of MetS factors present ( P = 0.001). After adjusting for age, reduced HDL cholesterol, and elevated triglycerides were the only factors significantly associated with IS. Increased IS was also significantly associated with hypogonadism. In an age‐ and testosterone (T)‐adjusted model, dyslipidemia was still associated with IS. To investigate whether metabolic factors could directly trigger prostate inflammation, we performed preliminary studies in myofibroblastic hBPH. Among the different factors, oxidized low‐density lipoprotein (oxLDL) showed the highest secretion of IL‐8 (>10‐fold)—a surrogate marker of prostate inflammation—as well as IL‐6, and bFGF. Co‐treatment with DHT significantly inhibited oxLDL‐induced secretion of IL‐8, whilst an AR‐antagonist, bicalutamide, reversed DHT effects. DHT suppresses oxLDL receptor (LOX‐1) expression. CONCLUSIONS Our data suggest that fats and insulin could have a detrimental effect on prostate health, boosting inflammation, a key pathogenic factor in BPH. Conversely, beneficial effects of DHT in counteracting lipid‐ and insulin‐induced prostatic alterations, suggest that T—via its conversion into DHT—may have unexpected beneficial effects on prostate health. Prostate 73: 789–800, 2013. © 2012 Wiley Periodicals, Inc.