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Brain Estradiol Content in Newborn Rats: Sex Differences, Regional Heterogeneity, and Possible de Novo Synthesis by the Female Telencephalon

Program in Neuroscience and Department of Physiology, University of Maryland at Baltimore, School of Medicine, Baltimore, Maryland 21201

Address all correspondence and requests for reprints to: Stuart K. Amateau, Department of Physiology, University of Maryland at Baltimore, School of Medicine, 655 West Baltimore Street, Bressler RB 5020, Baltimore, Maryland 21201. E-mail: samat001{at}umaryland.edu

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 aromatase inhibitor formestane. We found sexually dimorphic E₂ content in several regions of the newborn brain. At 2 h of life, there was significantly higher E₂ 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 post partum, 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.

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