In chapter 5 of the book »Androgens«, published in 1956, Dorfman writes: »Up to the present, no comprehensive blood studies are available«. This remark is meant to emphasize that we know very little about the neutral steroids of human blood. In order to help close this gap an investigation of the various fractions of human blood serum or plasma for its content of neutral steroids was started.
Die steigende Einsicht in viele Stoffwechselprozesse und die Anwendung neuer Methoden haben in den letzten Jahren zu einer weitgehenden Klärung der Wirkungsweise und auch der Konstitution der meisten kristallinen Steroidhormone der Nebennierenrinde (NNR) geführt. Im Gegensatz dazu sind unsere Kenntnisse über den noch verbleibenden wasserlöslichen Anteil, die sogenannte »amorphe Fraktion«, recht beschränkt. 1935 berichteten Pfiffner, Wintersteiner & Vars über eine bei ihrer Aufarbeitung anfallende Fraktion, die eine starke Wirkung im Überlebenstest am epinephrektomierten Hund aufwies. Sie stellte sich als eine sirupöse Substanz dar, die sich nicht weiter fraktionieren liess und der Kristallisation nicht zugängig war. Ihre Empfindlichkeit gegen Alkali, Mineralsäuren und Hitze sowie ihre Absorption bei 240 mμ liess die Autoren an das Vorliegen eines Gemisches von hauptsächlich α–β ungesättigten Ketonen denken. Ihre empirische Formel wurde mit HnC21O5 angegeben.Auffällig war weiter der relativ grosse Stickstoffgehalt des Sirups. Schwefelgehalt und Ascherückstand lagen im Bereich der Fehlergrenze. Erwöhnt sei hier die schon
In previous investigations different effects of various androgens (Testosterone, 5α-Di-hydrotestosterone and Androstandien-diol-diacetate) on cell metabolism and cell proliferation of ventral prostates and seminal vesicles in male rats have been found (Schmidt H. et al, Steroidologia 1 (1970) 94-104; Schmidt H. et al. 3rd Int. Congress Horm. Steroids, Hamburg 1970, Exc. Med. No. 210, p. 164). From these studies it was concluded that 5α-DHT is the main inducer of cell proliferation while the stimulation of cell metabolism may be related to other metabolites, i. e. Androstandion or 5α-An-drostan-3β,17α-diol. It therefore seemed of interest to investigate the action and meta-bolism of one of these metabolites, i. e. 5α-Androstan-3,17-dion, on a cellular level in the target tissues of male rats. Two types of experiments were performed. In one series immature castrated rats received 3 days a daily dose of 1 mg of this compound intra-peritoneally. DNA, RNA and protein content as well as enzyme activities of seminal vesicles and ventral prostates were determined. Compared to the data of a parallel study in which the same experimental schedule was performed with testosterone, an identical influence on cell proliferation and cell metabolism was found in the ventral prostates whereas in the seminal vesicles no effect on cell proliferation and a slight one on cell metabolism could be demonstrated. In a second experimental series 125 μCi 3H-5α-Androstandione was injected i. v. to adult male rats castrated 3 days previously. In the prostate the spec, radioactivity/g tissue found 30 min after the injection was 2 times higher than in the muscle, whereas no differences in specific radioactivity uptake could be measured between seminal vesicles and muscle. TLC revealed also differences in the distribution pattern of steroid metabolites in these target organs, specifically the amount of 5α-DHT found in the prostate superceeded that observed in the seminal vesicles by a factor 2. These results may explain the more pronounced influence of 5α-Androstan-3, 17-dion on the prostate. The lacking effect of 5α-Androstandion on cell proliferation in the seminal vesicles would agree with the relatively low conversion to 5α-DHT, which is assumed to have a strong proliferation effect.
SUMMARY Specific binding of [ 3 H]19-nortestosterone in the 100000 g cytosol of the rat bulbocavernosus/levator ani muscle (BCLA) and prostate was demonstrated by agargel electrophoresis at low temperature and compared qualitatively and quantitatively with the binding of tritiated testosterone and 5α-dihydrotestosterone (5α-DHT). Both tissues showed a greater binding affinity for 5α-DHT than for 19-nortestosterone, with testosterone binding the least well of the three. The relative binding affinities in the BCLA and prostate were: 19-nortestosterone: testosterone = 1·4, 19-nortestosterone: 5α-DHT = 0·7. The differences were statistically significant ( P < 0·02). The concentrations of receptor sites for 5α-DHT were 171 ± 20 ( s.d. ) fmol/mg prostatic cytosol protein and 24 ± 4 ( s.d. ) fmol/mg BCLA cytosol protein. The in-vitro metabolism of the three steroids in both tissues was also investigated by thin-layer chromatography. After incubating for 2 h at 0 °C the prostate was shown to reduce 26% of the 5α-DHT to androstanediols whilst the BCLA showed a 5% conversion. Testosterone was converted by the prostate to 5α-DHT (10%) and the androstanediols (6%) whilst the BCLA showed little activity in this respect. Comparing these in-vitro data with in-vivo findings from the literature, in both organs there is a positive correlation of the extent of binding in vitro to the stimulation of growth in vivo , bearing in mind that testosterone is metabolized to 5α-DHT in the prostate whilst in the BCLA, 5α-reductase is essentially absent.
The number of falsely positive values occurring in 12-channel analysis was determined in two groups of patients and reference individuals. It revealed that the portion of falsely positive values actually found was statistically significant beyond that calculated on the assumption of a binomial distribution. Partly distinct correlations of the parameters combined to a profile as well as clear deviations from the normal distribution have to be taken into consideration as reasons for this discrepancy between theory and reality. The results show that the application of the binomial distribution leads to statements which significantly differ from the conditions actually present.
