METABOLISM AND MODE OF ACTION OF ANDROGENS IN TARGET TISSUES OF MALE RATS

Abstract

ABSTRACT Either 1.3 μg [5,6-3H]5α-androstane-3,17-dione (27 Ci/mm), or 12 μg respectively 0.8μg [5,6-3H]5α-androstane-3α,17β-diol (3 Ci/mm), or 12μg respectively 0.8 μg ([5,6-3H]5α-androstane-3β,17β-diol (3 Ci/mm) were administered intravenously to normal adult rats on days 0, 3 and 12 after castration. 30 min after the injection the animals were sacrificed. Total radioactivity counting was performed on aliquots of extracts of blood, peripheral muscle, prostate and seminal vesicles. In the remaining extracts the steroids were isolated by repeated chromatography with and without derivative formation. The following results should be mentioned: 1. Compared to muscle an accumulation of radioactivity is found especially in the prostate on day 3 after castration. 2. Regarding the unconjugated metabolites in plasma no measurable interconversion of both diols has been observed, whereas androstanedione was efficiently metabolised to both diols and to androsterone. In muscle a substantial oxydation of both diols to the corresponding 17-keto-3-hydroxy derivative occurred. 3. In both target organs the three androgens were converted to 5α-DHT2) though in varying amounts. 4. From a calculation of the data available in both target organs a figure of 200 to 300 pg 5α-DHT/mg DNA has been obtained which is regarded as the receptor protein capacity limit. The influence of castration, of enzyme activities and of the chemical structure of the androgens administered on this figure is discussed.