Metabolism of 5 alpha reduced androgens by various tissues of the male rat.

Since an animal model for the study of peripheral androgen metabolism is needed, we studied the metabolism of 5 alpha-reduced androgens in various tissues of the rat. Labeled DHT and 3 alpha androstanediol (3 alpha diol) were added to tissue minces of male rat scrotal skin, muscle, prostate, or liver. Conversion ratios of the interconverting pair DHT in equilibrium with 3 alpha diol or the formation of the respective glucuronides (G) were determined over a 3 h period. Major differences in the activity and the oxidation/reduction relationship were observed between tissues. Scrotal skin was very active and balanced in the DHT in equilibrium with 3 alpha diol interconversion (31 and 33%/100 mg/3 h, respectively, whereas liver was minimally active (3.1/2.7%). 3 alpha reduction was prominent in muscle (37.0/2.7%), although 3 alpha oxidation was more active in prostate (6.0/31.5%). Steroid glucuronidation also differed in the various tissues. Sexual skin formed about 2% 3 alpha diol G, but much smaller amounts of DHTG. Liver, muscle, and prostate formed minimal (less than 0.2%) 3 alpha diol G, although liver synthesized 1.2% of DHTG. Addition of DHT or 3 alpha diol increased formation of the respective glucuronides by liver, whereas DHT blocked the synthesis of 3 alpha diol G, and 3 alpha diol markedly increased formation of 3 alpha diol G in skin. These studies indicate a similarity in DHT metabolism between rat and human sexual skin and a high rate of glucuronidation compared with other tissues. The pathway of 3 alpha diol G formation in skin is DHT----3 alpha diol----3 alpha diol G. Steroid 3 alpha oxidase is more active than 3 alpha reductase in muscle whereas 3 alpha oxidase predominates in prostate. This may be a mechanism whereby DHT levels and action as a nuclear androgen is favored in prostate, whereas testosterone is the major androgen in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)