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Abstract
Androgen acts via the androgen receptor and can play a critical role in the development and growth of the prostate and the pathophysiology of prostatic diseases. Testosterone is the most abundant circulating androgen and is converted to dihydrotestosterone (DHT), a more potent androgen, by steroid 5α-reductase. There are two 5α-reductase isoenzymes, type 1 and type 2, in humans and animals. Type 2 5α-reductase predominates in the prostate. While deficiency of type 2 5α-reductase causes male pseudohermaphroditism, increased DHT has been implicated in benign prostatic hyperplasia and prostate cancer. The aim of this article is to highlight the significance of 5α-reductase in the development and growth of the prostate and pathogenesis of prostatic diseases.
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Table 1.
Comparison of the two human 5α-reductase isoenzymes
| Type 1 5α-reductase | Type 2 5α-reductase | |
|---|---|---|
| Gene structure | 5 exons, 4 introns | 5 exons, 4 introns |
| Gene chromosome location | SRD5A1, 5p15 | SRD5A2, 2p23 |
| Size | 259 amino acids | 254 amino acids |
| Molecular weight (kilodaltons) | 29,462 (or 29,000) | 28,398 (or 28,000) |
| Homology | 49% | 49% |
| pH optima | Neutral to basic (6∼8.5) | Acidic to neutral (5.0∼5.5) |
| Testosterone affinity | Km=1∼5 (or 1.5) μM | Km=0.004∼1 (or 0.1∼1.0) μM∗ |
| Half life | 20∼30 hours | 20∼30 hours |
| Tissue distribution | Livers, sebaceous gland, nongenital | Prostate, genital skin, seminal vesicles, |
| skin, prostate, scalp, brain | epididymis, liver, hair follicles, uterus, breasts, brain, placenta | |
| Prostate level | Low | High |
| Prostate cell | ||
| Epithelial | ＋ | − |
| Basal | − | ＋ |
| Stromal | ＋ | ＋ |
| Prostate | ||
| Normal | ＋ | ＋ |
| BPH | ＋ | ＋ |
| Prostate cancer | ＋ | ＋ |
| Activity in 5αR deficiency | Normal | Mutated |
| Inhibitor | Dutasteride | Finasteride, dutasteride |
| Finasteride inhibition | Ki≥300 nM | Ki≥3∼5 nM |
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