A COMPARATIVE STUDY OF BINDING, METABOLISM AND ENDOGENOUS LEVELS OF ANDROGENS IN NORMAL, HYPERPLASTIC AND CARCINOMATOUS HUMAN PROSTATE

Abstract

14 Prostatic carcinomas (PCA), 14 benign prostatic hyperplasia (BPH) and 7 normal prostates (NPR) were investigated with respect to their 5α-dihydrotestosterone (DHT)-binding, in vitro metabolism of testosterone (T), DHT and 5α-androstane-3α,17β-diol (3α-diol), and tissue concentration of T, DHT and 3α-diol. Binding studies were performed by agar gel electrophoresis, metabolism was investigated by thin-layer chromatography, and the endogenous androgen concentrations were measured by radioimmunoassay. The main results were as follows: 1. Qualitatively no DHT-binding differences were found between PCA and BPH. 2. In PCA, a 2.5 times higher receptor concentration was found relative to BPH. 3. For both PCA and BPH, a positive correlation was found between plasma and cytosol sex hormone-binding globulin concentration. 4. Compared with BPH and NPR, the conversion T to DHT and of DHT to 5α-androstanediols was significantly decreased in PCA. 5. Compared with NPR, in BPH the ratio 5α-reduction to 3α(β)-reduction was significantly higher, mainly due to a reduced 3α(β)-reduction. 6. In NPR, compared with BPH and PCA, the ratio 5α-reduction to 3α(β)-reduction was significantly lower, mainly due to a relatively high 3α(β)-reduction. 7. The T concentration was significantly higher in PCA than in BPH or NPR. 8. The DHT concentration was significantly lower in NPR than in PCA or BPH; in this respect there were no significant differences between PCA and BPH. 9. The 3α-diol concentration was significantly higher in NPR than in BPH. High 3α-diol levels were also found in PCA. In conclusion, the NPR seems to be protected against excessive accumulation of T and DHT due to the shift of metabolism to the 5α-androstanediols. Compared with NPR, in PCA and BPH the androgen metabolism is shifted significantly to T and DHT, both of which have, in contrast to the 5α-androstanediols, a high affinity for the cytosol androgen receptor.