Estrogen receptor-β regulates tryptophan hydroxylase-1 expression in the murine midbrain raphe

Background: Distinct expression patterns of estrogen receptor (ER)-alpha and ER-beta are displayed in the murine central nervous system. ER-beta is the predominant form of the receptor expressed in the murine midbrain dorsal raphe nucleus (DRN). Tryptophan hydraxylase (TPH) is abundantly expressed in the serotoneigic neurons of the DRN and is regulated by estrogen in both the monkey and the guinea pig. Methods: In this study we used immunocytochemistry to show that ER-beta and TPH are colocalized in the serotonergic cells of the murine DRY We utilized the ER-alpha and ER-beta gene deletion mouse models and in situ hybridization to demonstrate that ER-beta is responsible for regulating TPH1 mRNA expression. Results. Estrogen increased TPH1 mRNA expression in the DRN of wild type and ER-alpha knockout mice (alpha-ERKO) but not ER-beta knockouts (beta-ERKO). Conclusions. These data indicate that ER-beta is responsible for mediating estrogen regulated TPH1 expression in the murine DRN.