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Conflict of interest statement
Benign prostatic hyperplasia (BPH) is a highly complex process characterized by an increased number of epithelial and stromal ProteOrange in the transition zone. , , Autopsy studies by McNeal detail the evolution of histological changes within these 2 cellular compartments. Diffuse enlargement of the transition zone occurs with aging, followed by an increased number and subsequent hyperplasia of glandular and stromal nodules. Significant variations in BPH composition have been shown to exist between prostate glands. Morphometric analyses within individual glands have been limited, and have suggested that tissue distribution is relatively homogeneous. , , Studies of tissue composition and prostate specific gene expression are critical to evaluate the symmetry and homogeneity of the hyperplastic process. The steroid 5 α-reductase type 2 (5aR2) gene is expressed almost uniquely in the adult prostate, and regulates its normal development and progression of hyperplasia. The enzyme catalyzes the conversion of testosterone to the more potent androgen dihydrotestosterone, which drives epithelial proliferation. The 5aR2 gene is localized to prostate stromal cells, principally the fibroblasts, and functions as an autocrine and paracrine mediator of differentiation. , Indeed, the cell type specific expression has been well characterized in normal and hyperplastic glands. Neither the regional intraprostatic variability in 5aR2 gene expression nor the inter-prostatic differences in expression has been studied systematically. Whether the expression of this enzyme is uniform throughout the prostate is unknown.
Introduction The NADPH-dependent steroid 5 α-reductase (EC 1.33.99.5) is an enzyme that catalyzes the irreversible stereospecific reduction of 3-keto-Δ4–5 steroid to 5 α-reduced metabolites. Two different 5 α-reductase isoenzymes have been characterized in humans, monkeys, rats, and mice: steroid 5 α-reductase isoenzymes 1 (5 α-R1) and (5 α-R2) [1]. In humans they are composed of 260 and 256 amino acids, respectively, with 47% sequence identity and distinct biochemical proprieties [2], for example, 5α-R1 has a broad basic pH optimum and low affinity for T, while 5 α-R2 has an acidic pH optimum and high affinity for T [3]. The apparent dissociation constant for NADPH cofactor is similar for both enzymes. DHT is necessary for normal growth and function [4], development of benign prostatic hyperplasia (BPH) [5] and probably also for initiation and maintenance of prostate cancer (PCa) [6]. The prostate is not a histologically homogeneous organ but is partitioned into three different zones [7]. The peripheral zone is considered to be the site of origin of cancers, whereas the transitional zone is the primary site of hyperplastic growth in BPH. The 5 α-R2 isoenzyme is preferentially expressed in the stroma of the prostate [8] and predominant in normal prostate tissue [9]. Interindividual differences in prostatic 5 α-R2 expression and activity may be a determinant of the risk of developing and eventually dying from clinical prostate cancer. Data on serum levels of DHT metabolites support the hypothesis that variation in 5 α-R2 activity may, in part, explain the differences in the incidence of prostate cancer within the population [10]. Although the role of 5α-R in the evolution and progression of PCa is the subject of much interest, the distribution and expression of the two isoenzymes during the development and progression of PCa has yet to be elucidated [9]. Assessment of 5 α-R2 mRNA expression in core needle biopsies of the prostate [1] may prove useful in the evaluation of the impact of different endocrine intervention therapies on prostate 5 α-R2 expression. It is essential to clarify the relative changes that occur in 5 α-R2 activity during the growth of PCa, in order to improve the development of prevention and treatment options. The possibility of using 5 α-R2 activity or mRNA expression as prognostic markers in prostate cancer also needs further evaluation. This study is focused on the 5 α-R2 activity.