Tryptophan hydroxylase mRNA levels are elevated by repeated immobilization stress in rat raphe nuclei but not in pineal gland.
Repeated stress triggers a wide range of adaptive changes in the central nervous system including the elevation of serotonin (5-HT) metabolism and an increased susceptibility to affective disorders. To begin to examine whether these changes are mediated by alterations in gene expression for tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, we quantitated its mRNA levels by competitive reverse transcription-polymerase chain reaction (RT-PCR). Repeated immobilization stress (2 h, 7 days) elicited a six- or ten-fold rise in TPH mRNA in median raphe nucleus (MRN) and dorsal raphe nucleus (DRN), respectively, without significantly altering TPH mRNA levels in the pineal gland. In contrast, there was little change in mRNA levels for GTP cyclohydrolase I (GTPCH), the rate limiting enzyme in synthesis of the tetrahydrobiopterin (BH4), the obligate cofactor for TPH. This is the first study to reveal stress-elicited activation of TPH gene expression.
Chamas
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Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595, USA.
Serova
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Sabban
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D000818:Animals; D006136:GTP Cyclohydrolase / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D008297:Male; D010870:Pineal Gland / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism*; D011903:Raphe Nuclei / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
D012333:RNA, Messenger; D014365:Tryptophan Hydroxylase; D006136:GTP Cyclohydrolase