Metabolic pathways for androstanediol formation in immature rat testis microsomes

Metabolic routes from progesterone to androstanediol in washed rat testicular microsomes were investigated, with special emphasis on the importance of 4-ene-3-oxosteroids, as well as the effect of a minimal effective dose of human chorionic gonadotropin on these transformations. Incubation of equimolar concentrations of a mixture of [14C]progesterone and 17 alpha-hydroxy[3H]progesterone resulted in a large preference of 17 alpha-hydroxyprogesterone over progesterone as substrate for androstanediol formation. Incubation of [3H]progesterone together with [14C]androstenedione resulted in the inhibition of C-17,20-lyase and in a low 14C/3H ratio in androstanediol, indicating the preference of progesterone over androstenedione as substrate for androstanediol production. When a mixture of 17 alpha-hydroxy[3H]progesterone and [14C]androstenedione was incubated with the microsomes, a more than 8-fold preference of 17 alpha-hydroxyprogesterone as substrate for androstanediol production was found. The minimal dose of human chorionic gonadotropin stimulated testosterone production but inhibited androstanediol formation and effected, in some instances, a change in the metabolic routes. It is concluded that androstanediol is produced preferentially through 17-hydroxylated C-21 steroids, and also, to a lesser extent, through C-19 steroids.