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

Background Distinct expression patterns of estrogen receptor (ER)-α and ER-β are displayed in the murine central nervous system. ER-β is the predominant form of the receptor expressed in the murine midbrain dorsal raphe nucleus (DRN). Tryptophan hydroxylase (TPH) is abundantly expressed in the serotonergic 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-β and TPH are colocalized in the serotonergic cells of the murine DRN. We utilized the ER-α and ER-β gene deletion mouse models and in situ hybridization to demonstrate that ER-β is responsible for regulating TPH1 mRNA expression. Results Estrogen increased TPH1 mRNA expression in the DRN of wild type and ER-α knockout mice (α-ERKO) but not ER-β knockouts (β-ERKO). Conclusions These data indicate that ER-β is responsible for mediating estrogen regulated TPH1 expression in the murine DRN.