Messenger RNA levels and enzyme activities of 5 alpha-reductase types 1 and 2 in human benign prostatic hyperplasia (BPH) tissue.
BACKGROUND
Benign prostatic hyperplasia (BPH) development requires testicular androgens and aging. The principle prostatic androgen is dihydrotestosterone (DHT). Testosterone is converted to DHT by the enzyme 5 alpha-reductase. Two distinct 5 alpha-reductase enzymes, types 1 and 2, have been identified. While some studies have suggested that type 2 isoenzyme predominates in the prostate, studies on the prostatic localization of the two isoenzymes are controversial. The purpose of this study was to determine the quantitative expressions of 5 alpha-reductase types 1 and 2 in BPH tissues.


METHODS
We examined the localizations of types 1 and 2 isoenzymes in BPH tissues using immunohistochemical staining and a real-time quantitative RT-PCR assay using the TaqMan system. We measured the enzyme activities of types 1 and 2 at pH values of 7.5 and 5.0, respectively.


RESULTS
Our immunohistochemical study showed that type 1 isoenzyme was expressed predominantly in epithelial cells, whereas type 2 isoenzyme was expressed in both stromal and epithelial cells. The real-time RT-PCR assay demonstrated that the copy numbers of type 1 isoenzyme mRNA were significantly higher than those of type 2 isoenzyme mRNA. There were significant associations between enzyme activity at pH 7.5 and type 1 isoenzyme mRNA expression, and between the activity at pH 5.0 and type 2 mRNA expressions.


CONCLUSIONS
We demonstrated that 5 alpha-reductase type 1 had a specific enzyme activity in the prostate, which supports the hypothesis that the type 1 isoenzyme may play a significant role in maintaining prostate enlargement along with the type 2 isoenzyme.
Shirakawa
Toshiro
T
Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. toshiro@med.kobe-u.ac.jp
Okada
Hiroshi
H
Acharya
Bishnu
B
Zhang
Zhujun
Z
Hinata
Nobuyuki
N
Wada
Yoshitaka
Y
Uji
Tatsuya
T
Kamidono
Sadao
S
Gotoh
Akinobu
A
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008297:Male; D011470:Prostatic Hyperplasia / Q000201:enzymology / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007527:Isoenzymes; D012333:RNA, Messenger; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase