title: Fat boosts, while androgen receptor activation counteracts, BPH-associated prostate inflammation.
abstract: 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.
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Vignozzi
authors.forename: Mauro
authors.initials: M
authors.lastname: Gacci
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cellai
authors.forename: Raffaella
authors.initials: R
authors.lastname: Santi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corona
authors.forename: Annamaria
authors.initials: A
authors.lastname: Morelli
authors.forename: Giulia
authors.initials: G
authors.lastname: Rastrelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Comeglio
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Sebastanelli
authors.forename: Elena
authors.initials: E
authors.lastname: Maneschi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Nesi
authors.forename: Cosimo
authors.initials: C
authors.lastname: De Nunzio
authors.forename: Andrea
authors.initials: A
authors.lastname: Tubaro
authors.forename: Edoardo
authors.initials: E
authors.lastname: Mannucci
authors.forename: Marco
authors.initials: M
authors.lastname: Carini
authors.forename: Mario
authors.initials: M
authors.lastname: Maggi
mesh_terms: D000368:Aged; D002460:Cell Line; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D011468:Prostatectomy / Q000379:methods; D011470:Prostatic Hyperplasia / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011472:Prostatitis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011944:Receptors, Androgen / Q000097:blood / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; D016207:Cytokines; D008077:Lipoproteins, LDL; D011944:Receptors, Androgen; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D012313:RNA