HUMAN PROSTATIC CARCINOMA: SIGNIFICANT DIFFERENCES IN ITS ANDROGEN BINDING AND METABOLISM COMPARED TO THE HUMAN BENIGN PROSTATIC HYPERTROPHY

Abstract

ABSTRACT The in vitro binding of 5α-dihydrotestosterone (5α-DHT), oestradiol-17β (Oe2) and methyltrienolone (R1881) was quantified in the 100 000 × g cytosol of 14 human prostatic carcinomas (PCA) by agargel electrophoresis, and compared, in part, to respective data obtained from human benign prostatic hypertrophy (BHP) samples. Furthermore, the in vitro metabolism of added 5α-DHT, testosterone (T) and 5α-androstane-3α,17β-diol in 10 of the 14 PCA, and for comparison, in 16 BPH samples, was analyzed by thin-layer chromatography, after a 30 min incubation period at 37°C. The main results were as follows: 1) Besides a sex hormone-binding globulin (SHBG) binding peak, in each of the 14 PCA cytosols a [3H]5α-DHT receptor binding could be demonstrated. By competition studies with unlabelled 5α-DHT a mean 5α-DHT receptor concentration of 30.9 fmol/mg cytosol protein (CP) (range 6.0–93.5) was calculated. In each of 7 cytosolic aliquots, incubated parallely with Oe2, an Oe2-binding to the receptor could be demonstrated, the concentration amounting to 8.4 fmol/mg CP (range 4.2–14.3). Simultaneous receptor quantification with R1881 in 4 cases revealed results, which are identical with the respective 5α-DHT data. 2) Dividing the PCA samples in group A (n = 6), consisting exclusively of adenocarcinomas, and group B (n = 8), consisting predominantly of a cribriform or cribriform and low differentiated tumour type, group B has a significantly (P < 0.05) higher assayable receptor concentration than group A. Comparing the total PCA with the BPH group, the former group has significantly (P < 0.04) higher levels of 5α-DHT receptor sites. 3) Comparing the mean cytosolic SHBG concentration of the PCA (93.2 fmol/mg CP) with the BPH (39.9 fmol/mg CP), the difference is significant (P < 0.01). Furthermore with respect to the PCA, there exists a significantly (P < 0.02) positive correlation between the plasmatic and cytosolic SHBG concentration. 4) The metabolic studies revealed that much more of the added T or 5α-DHT remains unmetabolized in the PCA than in the BPH. After T incubation, the amount of identified 5α-DHT plus 5α-androstanediols is on average 15 % lower in the PCA compared to the BPH. If 5α-DHT is added, the amount of identified 5α-androstanediols is on average 47 % lower in the PCA than in the BPH.