QUANTIFICATION OF ANDROGEN BINDING, ANDROGEN TISSUE LEVELS, AND SEX HORMONE-BINDING GLOBULIN IN PROSTATE, MUSCLE AND PLASMA OF PATIENTS WITH BENIGN PROSTATIC HYPERTROPHY

Abstract

ABSTRACT The in vitro binding of 5α-dihydrotestosterone (5α-DHT) in benign prostatic hypertrophy (BPH), rectus abdominis muscle and plasma of 14 patients was characterized and quantified by agargel electrophoresis. The respective endogenous tissue and plasma levels of 5α-DHT and testosterone (T) were determined by radioimmunoassay, and the plasmatic sex hormone-binding globulin (SHBG) concentration was estimated in the 14 patients by an (NH4)2SO4 precipitation technique. Finally the in vitro conversion of 5α-DHT to the 5α-androstanediols in the BPH at 0°C after a 20–24 h incubation period was analyzed by thin-layer chromatography. The main results were as follows: (1) In 12 out of 14 BPH cytosols three charcoal resistant binding peaks were found, of which peak 1 represents SHBG, peak 2 the specific receptor protein and peak 3 a binding protein with relatively high binding capacity and low affinity for 5α-DHT. In two cases peak 2 was absent. In 11 out of 14 muscle cytosols three binding peaks are also present, resembling those of the BPH. (2) The receptor peak is reduced on average 38 % by unlabelled 5α-DHT, 23 % by cyproterone acetate (CYAC) and 29 % by oestradiol. The parallel data for the SHBG peak are: 62% by 5α-DHT, 22% by CYAC and 49% by oestradiol. (3) From displacement studies with unlabelled 5α-DHT the average concentration of receptor was calculated to be 12.3 fmol/mg cytosol protein (CP) in BPH, and 3.6 fmol/mg CP in muscle. Under identical conditions 39.9 fmol SHBG/mg CP and 24.1 fmol/mg CP were found in the BPH and muscle, respectively. The mean values are significantly different (P < 0.001). In plasma a mean value of 4.0 × 10−8 mol SHBG/1 was found. (4) In the BPH on average 4.43 ng 5α-DHT/g tissue and 0.23 ng T/g tissue are present, in muscle 0.45 ng 5α-DHT/g tissue and 0.71 ng T/g tissue, in plasma 0.47 ng 5α-DHT/ml and 3.89 ngT/ml. (5) Statistical calculations revealed (a) a significantly (P < 0.05) negative correlation between the endogenous 5α-DHT and T tissue levels and the available 5α-DHT receptor sites in BPH cytosol, (b) a positive correlation between plasmatic SHBG concentration and the available SHBG concentration in BPH cytosol. (6) Compared to the rat prostate, where 36 % of the incubated 5α-DHT was converted at 0°C within 20–24 h into the 5α-androstanediols, in the BPH conversion to 5α-androstanediols was negligible.