Aim: Several studies have addressed the association between changes in the female sex hormones estrogen and progesterone levels and changes in parameters of periodontitis. In order to understand how these hormones affect periodontal health it is of major importance to obtain information on their physiological importance. We have previously shown that periodontal ligament cells (PDL cells) express estrogen receptor beta (ER beta) but not ER alfa immunoreactivity. The PDL cells express no immunoreactivity for progesterone receptors, suggesting that this cell type is not affected by progesterone. Treatment with a physiological concentration (100 nM) of estrogen increases DNA synthesis in human breast cancer cells but has no effect on PDL cell DNA and collagen synthesis. The purpose of this project is to investigate how and by which mechanisms estrogen influences structure and function of the periodontal ligament by affecting PDL cell functional properties. Methods: Human PDL cells were obtained from teeth extracted for orthodontic reasons. The cells were cultured from periodontal tissue explants and used in passages 3-5. Subcellular distribution of ER beta was determined by immunogold electron microscopy and confocal imagining using the mitochondrial selective probe MitoTracker and ER beta immunostaining. Expression of mitochondrial protein cytochrome c oxidase subunit I was investigated using Western blotting. The amounts of IL-6 and c-reactive protein (CRP) were determined by ELISA. Results: Confocal imaging revealed that ER beta immunoreactivity was distributed not only in the nucleus but also in the mitochondria. These results were confirmed using immunogold electron microscopy. Incubation with estrogen down-regulated the mitochondrial enzyme cytochrome c oxidase subunit I expression by about 30%, showing functional significance of mitochondrial ER. Preliminary data show that lipopolysaccharide (LPS) induces IL-6 but not CRP expression in PDL cells. The LPS induced IL-6 production is not affected by estrogen. Conclusion: Our data show that estrogen, preferably via ER beta, affects PDL cell functional properties, suggesting that estrogen and other ER specific ligands may modulate the periodontal tissue structure and function in health and disease.