Differential hormonal regulation of tryptophan hydroxylase-2 mRNA in the murine dorsal raphe nucleus.
BACKGROUND
Recently a novel tryptophan hydroxylase isoform (TPH2) was identified and shown to be highly expressed in the central nervous system (CNS). Hormonal effects on TPH2 mRNA expression in the rodent dorsal raphe nucleus (DRN) are unknown.


METHODS
In situ hybridization histochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were used to assess the effects of dexamethasone or estradiol on TPH2 mRNA levels in the DRN of C57/Bl6 mice.


RESULTS
Dexamethasone reduced TPH2 mRNA levels in the DRN of both ovx female and intact male mice. Reduction of TPH2 mRNA in the DRN was blocked by co-administration of mifepristone. Estradiol had no detectable effect on TPH2 mRNA levels in the DRN.


CONCLUSIONS
TPH2 mRNA is regulated by glucocorticoids but not estradiol in the mouse DRN. Glucocorticoid-mediated reduction of TPH2 message may have relevance to the etiology of major depression, psychotic major depression in particular, where elevated glucocorticoids are one hallmark of the disease.
Clark
Janet A
JA
Department of Molecular Endocrinology, Merck Research Laboratories, Merck & Company Inc., Rahway, New Jersey, USA. janet_clark@merck.com
Pai
Lee-Yuh
LY
Flick
Rosemarie Beth
RB
Rohrer
Susan P
SP
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D012333:RNA, Messenger / Q000096:biosynthesis*; D011903:Raphe Nuclei / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014365:Tryptophan Hydroxylase / Q000096:biosynthesis*; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects
D005938:Glucocorticoids; D006727:Hormone Antagonists; D006728:Hormones; D012333:RNA, Messenger; D015735:Mifepristone; D004958:Estradiol; D003907:Dexamethasone; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase