Dihydrotestosterone accumulation in genital skin fibroblasts derived from elderly men with prostatic hyperplasia

The conversion of testosterone to dihydrotestosterone (DHT) by 5 alpha-reductase and the interconversion between DHT and 5 alpha-Androstane-3 alpha,17 beta-diol (3 alpha-diol) by 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) were studied in fibroblasts derived from the genital skin of 15 prepubertal boys (2-10 yr), 17 young men (20-40 yr), 13 elderly men (60-78 yr) without clinically evident prostatic pathology, and 17 elderly men (61-88 yr) with benign prostatic hyperplasia (BPH). Respective DHT formations from testosterone (5 alpha-reduction) and 3 alpha-diol (3 alpha-HSOR oxidation) were not different among genital skin fibroblasts of the 4 groups. However, DHT degradation to 3 alpha-diol (3 alpha-HSOR reduction) was significantly lower in fibroblasts from elderly men with BPH than in those from the prepubertal boys (P less than 0.01), the young men (P less than 0.01), and the elderly men without BPH (P less than 0.05). 3 beta-HSOR reduction in fibroblasts of the BPH group was significantly lower (P less than 0.05) than in those of the elderly men without BPH; however, it did not differ from values for the prepubertal boys and the young men. (3 alpha + 3 beta)-HSOR reduction was also significantly lower (P less than 0.05) in the BPH group than respective values of the three other groups. These results indicate that DHT accumulation may occur in genital skin fibroblasts from elderly men with BPH, resulting from a shift in the overall balance of androgen metabolism, which favors the net formation of DHT.