Differential expression of 5α-reductase isoenzymes in the human prostate and prostatic carcinomas

✍ Scribed by Bonkhoff, Helmut; Stein, Ute; Aumüller, Gerhard; Remberger, Klaus

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 658 KB
• Volume: 29
• Category: Article
• ISSN: 0270-4137
• DOI: 10.1002/(sici)1097-0045(199610)29:4<261::aid-pros7>3.0.co;2-e

✦ Synopsis

BACKGROUND. Steroid 5a-reductase is essential for the intracellular accumulation of dihydrotestosterone (DHT), which mediates androgen effects on target tissue. METHODS. In the present study, we describe the differential expression and cellular localization of 5a-reductase 1 and 2 isoenzymes in the human prostate, and untreated and hormone-resistant prostatic carcinomas. The secretory epithelium of normal and hyperplastic glands showed strong nuclear 5a-reductase 1 reactivity. Accordingly, the DHT forming 5a-reductase process in secretory luminal cell types may be mediated predominantly by the type 1 isoenzyme. The androgen-independent basal cell layer variably expressed type 1 and 2 isoenzymes in nuclear and cytoplasmatic compartments. This suggests that circulating androgens are involved to control the basal cell layer, which represents the proliferative compartment of the human prostate. RESULTS. When compared with benign prostate tissue, increased 5a-reductase reactivity was detected in prostate cancer, particularly in high-grade tumors and androgen-insensitive states of the disease. In cancerous lesions, the type 1 isoenzyme tended to shift to the cytoplasm, while the nuclear staining remained unchanged or slightly increased. Referring to the type 2 isoenzyme, increased cytoplasmatic and nuclear enzyme activity was detected in malignant cells when compared with adjacent benign prostate tissue. Even endocrine differentiated tumor cells that consistently lacked the nuclear androgen receptor variably expressed 5a-reductase immunoreactivity. CONCLUSIONS. Although the functional sigruficance of the differential subcellular localization of type 1 and 2 isoenzymes is currently unknown, the present data suggest that prostate cancer retains the DHT forming 5a-reductase process in high-grade lesions and recurrent disease. Accordingly, circulating androgens may be still significant in these hormone-refractory malignancies.