Research Article
Sex Steroid Metabolism in Benign and Malignant Intact Prostate
Biopsies: Individual Profiling of Prostate Intracrinology
Daniele Gianfrilli,
1
Silvia Pierotti,
1
Riccardo Pofi,
1
Costantino Leonardo,
2
Mauro Ciccariello,
3
and Federica Barbagallo
1
1
Department of Experimental Medicine, Sapienza University, Viale del Policlinico 155A, 00161 Rome, Italy
2
Department of Urology, Sapienza University, 00161 Rome, Italy
3
Department of Radiology, Sapienza University, 00161 Rome, Italy
Correspondence should be addressed to Daniele Gianfrilli; daniele.gianfrilli@uniroma1.it
Received 2 May 2014; Accepted 18 June 2014; Published 13 August 2014
Academic Editor: Giovanni Luca Gravina
Copyright © 2014 Daniele Gianfrilli et al. his is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
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 proile of biopsies from patients with benign prostatic
hyperplasia (BPH) or cancer (PC), focusing on 17-hydroxy-steroid-dehydrogenases (17-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 identiied
three major patterns of conversion. he 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 17-HSD-isoenzymes-3/5. Conclusions. We developed an easy tool
to proile individual intraprostatic enzymatic activity by characterizing conversion pathways in an intact tissue environment.
In fresh biopsies we found that 17-HSD-isoenzymes and aromatase activities correlate with biological behaviour allowing for
morphofunctional phenotyping of pathology specimens and clinical monitoring of novel enzyme-targeting drugs.
1. Introduction
Prostate cancer is the most common cancer in men. An
increasing trend in prostate cancer incidence, a disease asso-
ciated with age, has been described and partially attributed
to better screening procedures [1] and awareness [2]. A
signiicant number of prostate cancers, however, remain
indolent and, if untreated, do not alter life quality and
expectancy. For this reason the burden of universal treat-
ment of conined asymptomatic disease should be weighed
against the economic socioeconomic costs of overtreatment,
the complications associated with the currently available
treatments (including androgen-deprivation therapy), and
the overall quality/life expectancy of afected subjects [3, 4].
Improvements in prostate cancer diagnosis, classiication,
and treatment witnessed in the past 20 years have not
been paralleled by improvement in preoperative prognostic
grading of the disease which still relies on morphological
appearance of random biopsies. A functional prognostic
presurgical characterization of the disease is needed to
identify those subjects who require aggressive treatment and
those who can be managed conservatively. Furthermore, a
function proiling of prostate tissue will also be very useful to
monitor unoperated patients during radiotherapy (RT) and
androgen-deprivation therapy (ADT) to follow up changes in
prostate tissue responsiveness and aggressiveness.
It is widely accepted that androgens play a central role
in the biology of the prostate. Estrogens, however, can
also modulate prostatic growth and development [5, 6].
Taken together, observations from many studies on murine
models imply that both androgens and estrogens are needed
to induce proliferative, precancerous lesions and prostate
Hindawi Publishing Corporation
BioMed Research International
Volume 2014, Article ID 464869, 8 pages
http://dx.doi.org/10.1155/2014/464869