A second tryptophan hydroxylase isoform, TPH-2 mRNA, is increased by ovarian steroids in the raphe region of macaques.
Recently, a second gene that codes for the rate-limiting enzyme in serotonin synthesis was found in brain, named tryptophan hydroxylase-2 (TPH-2). We sequenced overlapping segments (251 and 510 bp) of 5' monkey TPH-2 and questioned whether TPH-2 is regulated by estrogen (E) and progesterone (P) in serotonin neurons of macaques. Monkey TPH-2 was 97% homologous to human TPH-2 and 65% homologous to monkey TPH-1 in the coding region. Spayed monkeys were administered placebo, E-only, P-only, or E + P for 1 month via Silastic implants (n = 4/treatment) and the midbrain was utilized for TPH-2 in situ hybridization (ISH). Additional monkeys (n = 3/treatment) were used to determine the relative abundance of TPH-2 mRNA with quantitative (q) RT-PCR. In the ISH assay, all of the hormone treatments caused a significant and similar increase in TPH-2 mRNA optical density (fourfold; P < 0.004) and positive pixel area (twofold; P < 0.002) over spayed controls. Treatment with E or E + P for 1 month increased the relative abundance of TPH-2 mRNA over spayed controls in the qRT-PCR assay (ANOVA P < 0.05 and P < 0.007, respectively). In conclusion, ovarian steroids stimulate TPH-2 mRNA expression, which could in turn cause an increase in serotonin synthesis. This would impact many of the neural functions that are governed by serotonin.
Sanchez
Rachel L
RL
Division of Reproductive Sciences, Oregon National Primate Research Center, Beaverton, OR 97006, USA.
Reddy
Arubala P
AP
Centeno
Maria L
ML
Henderson
Jessica A
JA
Bethea
Cynthia L
CL
D000704:Analysis of Variance; D000818:Animals; D018076:DNA, Complementary / Q000378:metabolism; D003720:Densitometry / Q000379:methods; D004967:Estrogens / Q000097:blood / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007044:Hysterectomy / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008253:Macaca mulatta; D010052:Ovariectomy / Q000379:methods; D011374:Progesterone / Q000097:blood / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013256:Steroids / Q000097:blood / Q000494:pharmacology*; D014365:Tryptophan Hydroxylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D004967:Estrogens; D012333:RNA, Messenger; D013256:Steroids; D011374:Progesterone; D014365:Tryptophan Hydroxylase