Declaration of interest: Linda Vignozzi, Mauro Gacci, Ilaria Cellai, Annamaria Morelli, Paolo Comeglio, Marco Carini, Giovanni Corona, Gabriella Nesi, Raffaella Santi, Andrea Tubaro, Cosimo De Nunzio, Arcangelo Sebastianelli have no conflict of interest that could be perceived as prejudicing the impartiality of the research reported and have nothing to declare. Mario Maggi is a scientific consultant for Bayer Pharma A.G, Germany, Eli-Lilly Indianapolis, Indiana.
Article first published online: 28 NOV 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 73, Issue 8, pages 789–800, June 2013
How to Cite
Vignozzi, L., Gacci, M., Cellai, I., Santi, R., Corona, G., Morelli, A., Rastrelli, G., Comeglio, P., Sebastanelli, A., Maneschi, E., Nesi, G., De Nunzio, C., Tubaro, A., Mannucci, E., Carini, M. and Maggi, M. (2013), Fat boosts, while androgen receptor activation counteracts, BPH-associated prostate inflammation. Prostate, 73: 789–800. doi: 10.1002/pros.22623
Linda Vignozzi and Mauro Gacci contributed equally to this study.
- Issue published online: 25 APR 2013
- Article first published online: 28 NOV 2012
- Manuscript Accepted: 2 NOV 2012
- Manuscript Received: 4 SEP 2012
- Italian Minister of University, Research and Instruction. Grant Numbers: 2009WLNXNT_002, RBFR10VJ56_002
- metabolic syndrome;
- autoimmune response;
- prostate, LUTS
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.
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).
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.
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.