Because the primer sequences were not indicated, however, it is unclear which form of aromatase was amplified in that study. It is possible that the post-transcriptional FPL 64176 splicing to yield the short form of aromatase is regulated by E2, which could explain E2 regulation in Iivonen et al.. While a majority of studies in the brain have focused on hormonal modulation, the structure of the aromatase gene indicates multiple points of regulation, and aromatase is regulated by non-hormonal factors in peripheral tissues. For 5-Fluoro-2-deoxycytidine example, tissuespecific expression of aromatase is regulated through different promoter regions and alternative splicing. Cloning and structural characterization of the aromatase gene showed that the coding region spans 9 exons beginning with exon 2. There are multiple potential variants of exon 1, based on alternative transcription initiation sites, which are spliced into the 59- untranslated region ; however, the coding region, and thus the protein expressed, is the same. Although each of the alternative aromatase transcripts has been isolated from brains of both male and female mice, one transcript generates more than 85% of all aromatase transcripts in brains of both sexes. Whether differences in the 59-UTR lead to differential regulation of aromatase at the translational level has not yet been investigated in the brain. Interestingly, the promoter regions of the aromatase gene contain a wide array of responsive elements leading to differential regulation among tissues. For example, aromatase expression in the ovary is regulated primarily by cAMP, in the placenta by retinoids, in adipose tissue by cytokines such as IL-6 and IL-11, as well as TNF-alpha, and in osteoblasts by glucocorticoids. It is possible that aromatase expression in the brain is also regulated by one or several of these factors. We found that levels of long-form aromatase in non-reproductive brain regions such as the hippocampus were similar between males and females and not affected by gonadal/hormonal status. This is useful in the context of acute E2 modulation of synaptic transmission in the hippocampus, as it eliminates sex and gonadal/ hormonal status as factors that could influence the supply of locally synthesized estrogens through differential aromatase expression.