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

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Abstract
The in vitro binding of 5.alpha.-dihydrotestosterone (5.alpha.-DHT), estradiol-17.beta. (E2) and methyltrienolone (R1881) was quantified in the 100,000 .times. g cytosol of 14 human prostatic carcinomas (PCA) by agar gel electrophoresis, as compared, in part, to respective data obtained from human benign prostatic hypertrophy (BHP) samples. The in vitro metabolism of added 5.alpha.-DHT, testosterone (T) and 5.alpha.-androstane-3.alpha.,17.beta.-diol in 10 of the 14 PCA, and for comparison, in 16 BPH samples, was analyzed by TLC, after a 30 min incubation period at 37.degree. C. Besides a sex hormone-binding globulin (SHBG) binding peak, in each of the 14 PCA cytosols [3H]5.alpha.-DHT receptor binding could be demonstrated. By competition studies with unlabeled 5.alpha.-DHT a mean 5.alpha.-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 E2, E2-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 5.alpha.-DHT data. 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 tumor 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 5.alpha.-DHT receptor sites. 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). With respect to the PCA, a significantly (P < 0.02) positive correlation between the plasmatic and cytosolic SHBG concentration exists. The metabolic studies revealed that more of the added T or 5.alpha.-DHT remains unmetabolized in the PCA than in the BPH. After T incubation, the amount of identified 5.alpha.-DHT plus 5.alpha.-androstanediols is 15% lower in PCA compared to BPH. If 5.alpha.-DHT is added, the amount of identified 5.alpha.-androstanediols is 47% lower in PCA than in BPH.