Changes in fetal brain aromatase activity following in utero 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure in rats.

Aromatase catalyzes intraneuronal conversion of androgens to estrogens in the hypothalamus-preoptic area at a specific time during development. This local estrogen formation has a central role in sexual differentiation. To investigate the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on sexual differentiation, TCDD (800 and 1600 ng/kg) was orally administered to pregnant Holtzman rats on gestation day (GD) 15, and the change in brain aromatase activity of fetuses (GD20) and pups (postnatal day 2) was examined. Litter means of brain aromatase activity in the hypo-preoptic area of control fetuses were higher in males than in females (female/male ratio was 0.7). This ratio of aromatase activity increased in a TCDD-concentration dependent manner, reaching 1 at the higher dose. There was a similar change in aromatase activity in brains of pups (PND 2). These results suggest that in utero TCDD exposure induces demasculinization in male offspring by inhibiting the aromatase activity in the brain during central nervous system development.