Sex differences and estrogen regulation of BDNF gene expression, but not propeptide content, in the developing hippocampus.

Sex differences in adult brain function are frequently determined developmentally through the actions of steroid hormones during sensitive periods of prenatal and early postnatal life. In rodents, various cellular end points of the developing brain are affected by estradiol that is derived from the aromatization of circulating testosterone and/or synthesized within the brain. We have previously described a sex difference in neurogenesis in the hippocampus of neonatal rats that is modulated by estradiol. In this report, we examined a potential downstream regulator of the effects of estradiol on hippocampal cell proliferation by measuring gene expression of brain-derived neurotrophin (BDNF) in male and female neonatal rats in response to estradiol. Males had higher baseline BDNF gene expression in dentate gyrus and CA1 regions of the hippocampus compared with females. Neonatal administration of exogenous estradiol resulted in opposite effects on BDNF expression in these areas of the neonatal hippocampus, such that BDNF transcripts increased in CA1 but decreased in dentate. Blocking endogenous estradiol signaling by antagonizing estrogen receptors decreased BDNF expression in the dentate of males, but not females, and had no effect in CA1. Interestingly, this sex difference and response to estradiol was not mirrored by translational output, as no differences in BDNF precursor peptide were observed. The sex- and region-specific effects of estradiol on BDNF expression in the neonatal hippocampus suggest a complex functional relationship between these pleiotropic factors in regulating developmental neurogenesis.