Steroid secretion by in vitro perfused testes: testosterone biosynthetic pathways.

Alternative metabolic pathways for the biosynthesis of testosterone from pregnenolone exist in mammalian testes. The following experiments were designed to identify the preferred testosterone biosynthetic pathway in rat and rabbit testes. The experimental protocol included the infusion of steroidogenic reaction inhibitors and testosterone biosynthetic intermediates into testes perfused in vitro. Under these conditions, the testicular steroid secretions were a measure of specific reaction activities. Infusion of medrogestone (6,17-dimethyl-4,6-pregnadiene-3,20-dione, Ayerst), an inhibitor of delta5-4isomerization, permitted the reactions converting pregnenolone to androstenediol to be studied separately from those converting progesterone to testosterone. For example, the activity of the pregnenolone vector 17alpha-hydroxypregnenolone reaction was measured as the total of the 17alpha-hydroxypregnenolone, dehydroepiandrosterone, and androstenediol secreted by medrogestone-inhibited testes. The reactions convering delta5-3beta-hydroxysteroids to delta4-3-ketosteroids were studied in testes infused with SU-10603 (7-chloro-3,4-dihydro-2-[3-pyridyl]-1(2H)-naphthalenone. Ciba-Geigy), an inhibitor of 17alpha-hydroxylation and C-17, C-20 cleavage reactions. The results indicated that preferred testosterone biosynthetic pathways are present and different in rat and rabbit testes.