Brain estradiol content in newborn rats: Sex differences, regional heterogeneity, and possible de novo synthesis by the female telencephalon

Accurate assessment of gonadal steroid levels in the developing brain is critical for understanding naturally occurring steroid-mediated sexual differentiation as well as determining the physiological relevance of exogenous steroid treatments commonly used in the study of this phenomenon. Using RIA, we measured the estradiol (E₂) content of six regions of the developing brain immediately post partum, 1 d post partum, and after injection of exogenous estradiol benzoate, testosterone propionate, or the aromatose inhibitor formestane. We found sexually dimorphic E₂ content in several regions of the newborn brain. At 2 h of life, there was significantly higher E ₂ content in males vs. females in the frontal cortex, hypothalamus and preoptic area but not in the hippocampus, brainstem, or cerebellum. Surprisingly, the female hippocampus had significantly higher E₂ content than all other female regions examined. By d 1 postpartum, E₂ levels had decreased precipitously in most brain regions, and only the hypothalamus maintained a sex difference. Injection of female pups with estradiol benzoate raised tissue levels to that of the male in the hypothalamus but 2- to 3-fold higher in the other five regions. Testosterone administration increased E₂ content exclusively in the preoptic area, suggesting local variation in aromatase activity and/or substrate availability. Central administration of formestane decreased estrogen content in the male cortex, hypothalamus, and preoptic area. Formestane treatment also decreased endogenous E₂ in female cortex and hippocampus, suggesting de novo synthesis selectively in these brain regions. These data corroborate and extend previous findings of sex differences in brain E₂ levels perinatally and reveal an unexpected regional heterogeneity in E₂ synthesis and/or metabolism.