Estrogen metabolism in neural tissues of six-day-old rats

In vitro incubation of pituitary, hypothalamus and cerebral cortex from 6-day-old rats with [6,7-3H]estradiol revealed that estradiol is actively metabolized in these tissues. Pituitary was found to be more active than hypothalamus and cerebral cortex in metabolizing estradiol in these animals. Covalent binding of estradiol to acid-precipitable proteins was observed in all these tissues from both sexes. While there was no significant sex difference in protein binding of estradiol in any of the tissues tested, treatment with progesterone or estradiol valerate increased protein binding. 2- and 16-hydroxylation and 17 beta-oxidation were demonstrated in all the tissues tested. While there were no significant sex differences observed in 2,16-hydroxylation, 17 beta-oxidation appeared to be more in males. Progesterone treatment of males increased 2-hydroxylation of estradiol 4-fold in pituitary and doubled the levels in hypothalamus. 16-Hydroxylation and 17-oxidation were also elevated significantly in pituitary and hypothalamus by progesterone treatment. Estradiol valerate treatment, however, decreased 2-hydroxylation and 16-hydroxylation in pituitary and hypothalamus; 17-oxidation was increased in pituitary. These results suggest that the estradiol metabolism, and especially 2-hydroxyestradiol formation, can be increased by progesterone and thereby mediate antagonistic effect of progesterone on estrogen-mediated brain sexual differentiation.