• The Korean Journal of Physiology and Pharmacology
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• v.3 no.5
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• pp.501-505
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• 1999

Tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis, is primarily expressed in serotonergic neurons of the raphe nuclei. Simple tandem repeat polymorphisms, typically one to four nucleotides long, are tandemly repeated several times and often characterized by many alleles. To identify the presence of polymorphic repeats, we sequenced the 5'-upstream region of the mouse TPH gene. For the detection of any allelic variants, polymerase chain reaction, nonisotopic single-strand conformation polymophism, and DNA sequencing analyses of the tandem repeat sequences were performed using genomic DNA extracted from 60 ICR mice. Two dinucleotide repeats, $5'-(AC/TG)_{22}-3'$ and $5'-(GT/CA)_{17}3',$ were identified at approximately - 5.7 kb and - 3.4 kb upstream from the transcriptional initiation site of the mouse TPH gene, respectively. Minor allelic variants, $5'-(AC/TG)_{21}-3'$ and $5'-(GT/CA)_{18}-3',$ were observed in heterozygous pairs from 3 of 60 and 1 of 60 ICR mice, respectively. The identification of these microsatellites in the mouse TPH promoter raises the possibility that identical and/or other polymorphic sequences might exist in the upstream region of the human TPH gene.

• Journal of Nutrition and Health
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• v.33 no.1
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• pp.5-12
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• 2000

The control of food intake is a complex phenomenon caused by interactions between central and peripheral control mechanisms. The hypothalamic and brain stem regions have been identified as centers for food intake and energy expenditure in animals and humans. Of these, the ventromedial and lateral hypothalamic areas are involved in the control of food intake. Also, large amounts of neurotransmitters known to be involved in feeding are present in the hippocampus. Paricularly, tryptophan hydroxylase(TPH), known as a factor in the control of food intake, is present in high levels in the paraventricular nucleus of the hypothalamus and the hippocampus. In this study, TPH expression levels in the hypothalamic and hippocampal regions of fasting, anorexia mutant, and control mice were compared using RT-PCR and immunohistochemical methods. Differences in body weight among the fasting, anorexia mutant, and control groups wire observed. No statistical significance was noted in the number of TPH-immunoactivity in the hypothalamic nuclei, but relatively higher populations of such fibers were observed in the fasting group : the control group yielded samples with an overall value of 170.3${\pm}$3.5 in terms of immunoreactivity-induced optical density, whereas the fasting group yielded a value of 168.3${\pm}$2.6, and the anorexia mutant group 171.3${\pm}$0.8(lower values represent higher immunoreactivity), In fasting mice, stained neuronal bodies were observed in the CA3 and dentate gyrus regions of the hippocampus, which was different from the hippocampal regions of the control and anorexia mutant mice. The RT-PCR procedures were performed using whole brains, precluding any statistically noticeable findings in relation to specific regions, although the fasting and anorexia mutant groups showed 123.3% and 102.9%, respectively, of the TPH mRNA level in the control. The overall results present evidences of the role of TPH in the decrease in food intake during fasting caused by exogenic factors and in genetically acquired anorexia. (Korean J Nutrition 33(1) : 5-12, 2000)