Endogenous levels of 5 alpha-reduced progestins and androgens in fetal vs. adult rat brains

5 Alpha-reduced metabolites of certain steroids have been shown to have important functions in adult brains and may play a role in brain development. To assess which 5 alpha-reduced steroid metabolites may have an impact during development, endogenous levels of 5 alpha-reduced androgens and progestins and their parent hormones were measured in male and female fetal brains over the last 5 days of gestation. These levels were compared to levels measured in adult male and female brains (evaluated at different stages of the estrous cycle). Neither the brain levels of parent hormones nor of their 5 alpha-reduced metabolites varied as a function of fetal sex or of gestational age. Therefore, the data from the two sexes were combined. In fetal brains, the levels of the progesterone reduced metabolites were 20-fold higher than levels of progesterone itself whereas levels of testosterone reduced metabolites were 10-fold lower than testosterone levels. In contrast to fetal brain, conversion of progesterone to reduced metabolites was much lower in adult brain, but the level of 5 alpha-reduced androgens was 3–10-fold higher than the level of testosterone in all adult tissue, indicating more conversion of androgen to 5 alpha-reduced metabolites in adult than in fetal brains. These results imply that the reduction of progesterone to reduced metabolites may play a critical role in brain development.