Aromatization and 19-hydroxylation of androgens by rat brain cytochrome P-450

The oxidative metabolism of androgens in the rat brain includes aromatization preceded by the requisite 19-hydroxylation. We have examined the transformation of [19-C3H3]androstenedione and [4-14C]testosterone by the semipurified cytochrome P-450 fraction of the rat brain. [19-C3H3]Androstenedione generated tritiated water and formic acid in a ratio of 8 to 1 indicating that 19-hydroxylation in the brain far exceeds that necessary for aromatization. This was confirmed by the results of the 14C-testosterone incubation in which the 14C labeled 19-hydroxy and 19-oxo derivatives which were isolated exceeded the yield of 14C-estrogens by several fold. Thus the rat brain has the capacity to form in situ 19-hydroxylated androgens which are not available to it from the circulation.