Recovery of Free Androgens in the Rat Prostate In Vivo and In Vitro after Treatment with Orally Active Testosterone Undecanoate (TU)

Abstract

Short-term castrated rats were sacrificed at different time intervals after oral administration of [3H-] labeled TU [testosterone]. Blood and organs were collected and measured for total radioactivity uptake. At the time of peak values of radioactivity the vivo metabolite pattern was investigated by TLC. In vitro studies were performed in plasma, muscle and prostate cytosol. The radioactivity uptake into plasma and prostate in vivo reached a 1st maximum 2 1/2 h after oral administration of TU. A 2nd peak appeared after 5 h in the prostate. While only 16% of the total plasma radioactivity appeared in the non-esterified fraction, the tissues contained 69-71%. In plasma, the bulbocavernosus/levator ani muscle and in the skeletal muscle, free testosterone was the main unesterified androgen (14-28%). Prostate and seminal vesicles contained primarily 5.alpha.-DHT (47 and 34%, respectively). Further metabolites were found in the fractions of 17.beta.-hydroxy-5.alpha.-androstanediol, epiandrosterone, androsterone, 4-androstenedione and 5.alpha.-androstanedione. After incubation in vitro with TU, prostate and muscle cytosol contained significant amounts (39 and 17%, respectively) of free androgens. Apparently peripheral organs and the prostate itself are capable of cleaving the undercanoic ester and the biological action of TU is exerted by unesterified androgens which occur in a pattern similar to that obtained after i.v. injection of free testosterone.