17 beta-Estradiol is synthesized de novo in the rat hippocampus. However, the regulatory mechanism of hippocampal estradiol synthesis has remained unclear. We investigated the effects of social isolation on rat hippocampal estradiol synthesis. Rats were divided into two groups: social isolation and pair housed group. Socially isolated rats were housed individually while pair housed rats were housed two per cage for 8 weeks. Social isolation activated the transcription of neurosteroidogenic molecules, including steroidogenic acute regulatory protein (StAR) and CYP19 (cytochrome P450arom). These two molecules are involved in the regulatory Step for steroidogenesis and final step of estradiol synthesis. In contrast, the mRNA levels were not affected in rat olfactory bulb. The hippocampal estradiol content was increased in accordance with the increased mRNA levels. The hippocampal estradiol content exhibited correlations with the StAR and P450arom mRNA levels. These data suggest that social isolation may enhance de novo estradiol synthesis in the hippocampus. (C) 2008 Elsevier Inc. All rights reserved.