The extragonadal origin of 5 alpha-reduced androgens in the peripheral circulation of the adult male rabbit.

The extragonadal source of the high levels of 5 alpha-reduced androgens in the peripheral blood of the male rabbit has been investigated. Adult 3-day castrated rabbits each received a single intravenous injection of 3H-labelled testosterone, and blood plasma was collected at various intervals thereafter. Two h post injection, animals were killed, various accessory sex organs and peripheral tissues removed, and radioactively labelled testosterone and its metabolites quantified by radio-gas-liquid chromatography (radio-g.l.c.). Five min after the injection of 3H-labelled testosterone, the major labelled metabolite in blood plasma was 5 alpha-dihydrotestosterone with small amounts of 3 alpha/3 beta-androstanediols and androstenedione. After 2 h significant quantities of 3H-labelled 5 alpha-dihydrotestosterone had accumulated in the accessory sex organs, whereas only small amounts were found in "non-sexual" peripheral tissues such as skeletal muscle. However, substantial amounts 3-day castrated rabbits, when they were incubated in vitro with 3H-labelled testosterone; the most active were skeletal muscle, liver and abdominal skin. Some formation of 3 alpha/3 beta-androstanediols occurred in all tissues. It is concluded that in the male rabbit skeletal muscle and skin are likely to be a significant extragonadal source of 5 alpha-reduced androgens for the maintenance of accessory sex organs such as the prostate and epididymis, which have low 5 alpha-reductase activity but a high capacity to retain 5 alpha-dihydrotestosterone.