Fat boosts, while androgen receptor activation counteracts, BPH‐associated prostate inflammation

L Vignozzi, M Gacci, I Cellai, R Santi, G Corona… - The …, 2013 - Wiley Online Library
L Vignozzi, M Gacci, I Cellai, R Santi, G Corona, A Morelli, G Rastrelli, P Comeglio…
The Prostate, 2013Wiley Online Library
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 …
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.
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