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

Abstract

ABSTRACT Either 0.7 μg [1,2-3H] testosterone* (51 Ci/mm) or 0.8 μg [1,2-3H] 5α-dihydrotestosterone (44 Ci/mm) was administered intravenously to normal adult male rats 3, 7, and 12 days after castration. 30 min after the injection, the animals were sacrificed. Total radioactivity counting was performed on aliquots of extracts of blood, peripheral muscle, prostates and seminal vesicles. In a first TCL the extracts were separated into five fractions. Further purification by acetylation and repeated chromatographic procedures revealed, that fraction C consisted of about 90 % of testosterone, fraction D of varying amounts of 5α- and 5β-DHT, fraction E of androstanedione and androstenedione, and fraction B mainly of androstanediols. The following results should be mentioned: 1. The radioactivity uptake by the accessory sex organs was significantly higher than that of skeletal muscle. The highest values were found on day 3 after castration. 5α-DHT under all conditions produced higher concentrations in the target tissues than testosterone, whereas in skeletal muscle the opposite was found. 2. After testosterone administration testosterone was very efficiently converted to 5α-DHT in target organs. Nevertheless substantial amounts of testosterone and of androstanedione and androstanediols are present. In blood, however, only small amounts of labelled 5α-DHT were found. After 5α-DHT administration, in target organs, 5α-DHT was converted to androstanedione and androstanediols up to about 20%. In blood the bulk of radioactivity was related to the androstanediol fraction. No conclusion therefore can be drawn from the data obtained in blood on the metabolic events occurring in the target organs. 3. The sequence of metabolic events in the target tissues supports the concept of a preferred 17-hydroxy pathway and a lack of 5β-reductase.