Differential expression of 5-alpha reductase isozymes in the prostate and its clinical implications

Kai Wang, Dong-Dong Fan, Song Jin, Nian-Zeng Xing, Yi-Nong Niu, Kai Wang, Dong-Dong Fan, Song Jin, Nian-Zeng Xing, Yi-Nong Niu

Abstract

The development of human benign or malignant prostatic diseases is closely associated with androgens, primarily testosterone (T) and dihydrotestosterone (DHT). T is converted to DHT by 5-alpha reductase (5-AR) isozymes. Differential expression of 5-AR isozymes is observed in both human benign and malignant prostatic tissues. 5-AR inhibitors (5-ARI) are commonly used for the treatment of benign prostatic hyperplasia (BPH) and were once promoted as chemopreventive agents for prostate cancer (PCa). This review discusses the role of the differential expression of 5-AR in the normal development of the human prostate and in the pathogenesis and progression of BPH and PCa.

Figures

Figure 1
Figure 1
Pathway of steroid biosynthesis and the conversion of T to DHT by 5-AR. C21 precursors (pregnenolone and progesterone) are converted to C19 adrenal androgens (DHEA and androstenedione) by sequential hydroxylase and lyase activities. Circulating adrenal androgens enter the prostate and can be converted to T or androstanedione by a series of reactions involving the activity of 3β and 17β enzymes. T is then converted to the potent androgen DHT by the activity of 5-AR. 17α: 17α-hydroxylase; 17,20: 17,20-lyase; 21: 21-hydroxylase; 3β: 3-HSD (hydroxysteroid dehydrogenase); 17β: 17-HSD (hydroxysteroid dehydrogenase); DHEA: dihydroepiandrosterone; AKR1C: aldo-keto reductase; 3α-diol: 5α-androstane-3α, 17β-diol; 3β-diol: 5α-androstane-3β, 17β-diol.

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