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Posttranslational regulation of TPH1 is responsible for the nightly surge of 5‐HT output in the rat pineal gland
Author(s) -
Huang Zheping,
Liu Tiecheng,
Chattoraj Asamanja,
Ahmed Samreen,
Wang Michael M.,
Deng Jie,
Sun Xing,
Borjigin Jimo
Publication year - 2008
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2008.00627.x
Subject(s) - pineal gland , medicine , endocrinology , melatonin , tryptophan hydroxylase , biology , serotonin , circadian rhythm , stimulation , receptor , serotonergic
Serotonin (5‐hydroxytryptamine, 5‐HT), a precursor for melatonin production, is produced abundantly in the pineal gland of all vertebrate animals. The synthesis of 5‐HT in the pineal gland is rate limited by tryptophan hydroxylase 1 (TPH1) whose activity displays a twofold increase at night. Earlier studies from our laboratory demonstrate that pineal 5‐HT secretion exhibits dynamic circadian rhythms with elevated levels during the early night, and that the increase is controlled by adrenergic signaling at night. In this study, we report that (a) 5‐HT total output from the pineal gland and TPH1 protein levels both display diurnal rhythms with a twofold increase at night; (b) stimulation of cAMP signaling elevates 5‐HT output in vivo; (c) 5‐HT total output and TPH1 protein content in rat pineal gland are both acutely inhibited by light exposure at night. Consistent with these findings, molecular analysis of TPH1 protein revealed that (a) TPH1 is phosphorylated at the serine 58 in vitro and in the night pineal gland; and (b) phosphorylation of TPH1 at this residue is required for cAMP‐enhanced TPH1 protein stability. These data support the model that increased nocturnal 5‐HT synthesis in the pineal gland is mediated by the phosphorylation of TPH1 at the serine 58, which elevates the TPH1 protein content and activity at night.