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Messenger Ribonucleic Acid Levels of Steroid 5-Reductase 2 in Human Prostate Predict the Enzyme Activity¹

Departments of Medical Laboratory Sciences and Technology (T.G.S., C.B., B.A., A.R.), Karolinska Institutet, Division of Clinical Pharmacology, Huddinge University Hospital, SE-14186, Huddinge; Stockholm Pathology and Cytology (L.E.), Karolinska Hospital, SE-171 76, Stockholm; and Urology (E.B., B.J.N.), Uppsala University Hospital, SE-751 85, Uppsala, Sweden

Address all correspondence and requests for reprints to: Torbjörn Söderström, Department of Clinical Pharmacology, Huddinge University Hospital C168, S-141 86 Huddinge, Sweden. E-mail: torbjorn.soderstrom{at}medsci.uu.se

Testosterone is converted to dihydrotestosterone by 5-reductase2 in the prostate. Dihydrotestosterone controls cell division, and interindividual differences in prostatic 5-reductase 2 expression and activity may be a determinant of the risk of developing prostate cancer. However, little is known about interindividual differences in intraprostatic hormonal activity in vivo. To determine whether 5-reductase-specific messenger RNA (mRNA) is predictive of 5-reductase activity in prostatic tissue, we analyzed 30 prostatic tissue specimens from 15 Caucasian patients, 47–82 yr old. The mRNA was measured by RT-PCR. Five specimens consisted of cancer, whereas the remaining 25 were derived from benign prostate hyperplasia (BPH).

We found a strong association between enzyme activity at pH 5.5 and the 5-reductase 2-specific mRNA expression when expressed on the basis of ß-actin [Spearman’s rank-correlation coefficient (r_s) = 0.81; 95% confidence interval, 0.64–0.91; P < 0.0001]. The expression of 5-reductase 2-specific mRNA in the cancer specimens was significantly lower than in the BPH tissue (P = 0.03). There was no difference in the expression of 5-reductase 1-specific mRNA in the cancer specimens, compared with BPH (P = 0.56). The strong association between 5-reductase activity at pH 5.5 and the 5-reductase 2-specific mRNA expression makes it possible to predict prostatic 5-reductase activity using core needle biopsies.

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