Estrogen receptor-beta 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 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-beta and TPH are colocalized in the serotonergic cells of the murine DRN. 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.
Gundlah
Chrisana
C
Synaptic Pharmaceutical Corporation, Paramus.
Alves
Stephen E
SE
Clark
Janet A
JA
Pai
Lee-Yuh
LY
Schaeffer
James M
JM
Rohrer
Susan P
SP
D000818:Animals; D002478:Cells, Cultured; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology; D047629:Estrogen Receptor beta / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008636:Mesencephalon / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D010052:Ovariectomy; D011903:Raphe Nuclei / Q000201:enzymology / Q000378:metabolism*; D012701:Serotonin / Q000502:physiology; D014365:Tryptophan Hydroxylase / Q000096:biosynthesis*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012701:Serotonin; C487801:Tph1 protein, mouse; D014365:Tryptophan Hydroxylase