IN-VITRO STUDIES ON TESTOSTERONE AND 5α-DIHYDROTESTOSTERONE BINDING IN BENIGN PROSTATIC HYPERTROPHY (BPH)

1973 ◽  
Vol 71 (4_Suppl) ◽  
pp. S69
Author(s):  
P. Steins ◽  
H. J. Hollmann ◽  
H. Schmidt ◽  
K. D. Voigt
1974 ◽  
Vol 75 (4) ◽  
pp. 773-784 ◽  
Author(s):  
P. Steins ◽  
M. Krieg ◽  
H. J. Hollmann ◽  
K. D. Voigt

ABSTRACT The cytosol fractions of prostatic adenoma and of the rectus abdominis muscle, together with the respective plasma samples were investigated in 13 patients in order to clarify whether or not there is an androgen receptor in human benign prostatic hypertrophy. The following methods were used: High speed ultracentrifugation in a sucrose gradient and agar gel electrophoresis at low temperature, of the 100 000 g supernatants after in vitro incubation with 3H-testosterone, 3H-5α-dihydrotestosterone, and 3H-oestradiol-17β. In parallel experiments the supernatants were heated to 45°C for 1 h before the steroid incubation. Displacement experiments with a 100–500-fold excess of various cold androgens. In the supernatants as well as in the plasma samples the total protein concentration was measured by the biuret reaction. The concentration of albumin and of immunoglobulin G (IgG) in the various biological fluids was determined by quantitative immuno diffusion. After charcoal stripping the binding of testosterone and of 5α-dihydrotestosterone was estimated quantitatively and correlated to the plasma contamination. By the methods used no physico-chemical differences in the androgen binding properties of plasma and of prostate cytosol were observed. However, in any individual cytosol a higher 5α-DHT binding than could be related to the plasma contamination was obtained. The question therefore remains open, as to whether the augmented 5α-dihydrotestosterone binding relates to a cellular increase of sex hormone binding globulin (SHBG) or to androgen receptors which do not show up clearly under the experimental conditions used.


1977 ◽  
Vol 86 (1) ◽  
pp. 200-215 ◽  
Author(s):  
M. Krieg ◽  
W. Bartsch ◽  
S. Herzer ◽  
H. Becker ◽  
K. D. Voigt

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.


1984 ◽  
Vol 102 (1) ◽  
pp. 73-76 ◽  
Author(s):  
A. Leake ◽  
G. D. Chisholm ◽  
F. K. Habib

ABSTRACT The interaction between prolactin and zinc was examined in vitro in the human prostate gland. The results indicated that prolactin did not modulate the acute uptake of zinc into benign prostatic hypertrophy tissue whereas zinc, in contrast, increased the uptake of prolactin into the prostate gland. Our study further showed that the augmented uptake of prolactin by zinc was partly due to an increase in the non-specific binding properties of the peptide hormone. We were also able to demonstrate that the specific binding of 125I-labelled human prolactin to the receptor was reduced in the presence of zinc by a competitive mechanism. J. Endocr. (1984) 102, 73–76


1978 ◽  
Vol 88 (2) ◽  
pp. 397-407 ◽  
Author(s):  
M. Krieg ◽  
I. Grobe ◽  
K. D. Voigt ◽  
E. Altenähr ◽  
H. Klosterhalfen

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.


2006 ◽  
Vol 15 (04) ◽  
pp. 245-257 ◽  
Author(s):  
H. J. Rolf ◽  
K. G. Wiese ◽  
H. Siggelkow ◽  
H. Schliephake ◽  
G. A. Bubernik

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