title: Sex steroid metabolism in benign and malignant intact prostate biopsies: individual profiling of prostate intracrinology.
abstract: In vitro studies reveal that androgens, oestrogens, and their metabolites play a crucial role in prostate homeostasis. Most of the studies evaluated intraprostatic hormone metabolism using cell lines or preprocessed specimens. Using an ex vivo model of intact tissue cultures with preserved architecture, we characterized the enzymatic profile of biopsies from patients with benign prostatic hyperplasia (BPH) or cancer (PC), focusing on 17β-hydroxy-steroid-dehydrogenases (17β-HSDs) and aromatase activities. Samples from 26 men who underwent prostate needle core biopsies (BPH n = 14; PC n = 12) were incubated with radiolabeled (3)H-testosterone or (3)H-androstenedione. Conversion was evaluated by TLC separation and beta-scanning of extracted supernatants. We identified three major patterns of conversion. The majority of BPHs revealed no active testosterone/oestradiol conversion as opposed to prostate cancer. Conversion correlated with histology and PSA, but not circulating hormones. Highest Gleason scores had a higher androstenedion-to-testosterone conversion and expression of 17β-HSD-isoenzymes-3/5. Conclusions. We developed an easy tool to profile individual intraprostatic enzymatic activity by characterizing conversion pathways in an intact tissue environment. In fresh biopsies we found that 17β-HSD-isoenzymes and aromatase activities correlate with biological behaviour allowing for morphofunctional phenotyping of pathology specimens and clinical monitoring of novel enzyme-targeting drugs.
authors.affiliation: Department of Experimental Medicine, Sapienza University, Viale del Policlinico 155A, 00161 Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Gianfrilli
authors.affiliation: Department of Experimental Medicine, Sapienza University, Viale del Policlinico 155A, 00161 Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pierotti
authors.affiliation: Department of Experimental Medicine, Sapienza University, Viale del Policlinico 155A, 00161 Rome, Italy.
authors.forename: Riccardo
authors.identifier: 0000-0001-7808-5735
authors.initials: R
authors.lastname: Pofi
authors.affiliation: Department of Urology, Sapienza University, 00161 Rome, Italy.
authors.forename: Costantino
authors.initials: C
authors.lastname: Leonardo
authors.affiliation: Department of Radiology, Sapienza University, 00161 Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ciccariello
authors.affiliation: Department of Experimental Medicine, Sapienza University, Viale del Policlinico 155A, 00161 Rome, Italy.
authors.forename: Federica
authors.identifier: 0000-0002-2972-370X
authors.initials: F
authors.lastname: Barbagallo
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000368:Aged; D000728:Androgens / Q000378:metabolism; D001141:Aromatase / Q000378:metabolism*; D001706:Biopsy; D004967:Estrogens / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000201:enzymology* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D012725:Sexual Behavior; D013739:Testosterone / Q000378:metabolism
chemical_list: D000728:Androgens; D004967:Estrogens; D013739:Testosterone; D015067:17-Hydroxysteroid Dehydrogenases; D001141:Aromatase