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.

中文翻译：

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TPH1 的翻译后调节是夜间大鼠松果体 5-HT 输出激增的原因。

血清素（5-羟色胺，5-HT）是产生褪黑激素的前体，在所有脊椎动物的松果体中大量产生。松果体中 5-HT 的合成受到色氨酸羟化酶 1 (TPH1) 的限制，其活性在夜间增加两倍。我们实验室的早期研究表明，松果体 5-HT 分泌表现出动态昼夜节律，在夜间升高水平，并且这种增加是由夜间肾上腺素信号控制的。在这项研究中，我们报告说 (a) 松果体的 5-HT 总输出和 TPH1 蛋白水平都显示出昼夜节律，夜间增加两倍；(b) cAMP 信号的刺激提高了体内 5-HT 的输出；（ c ）大鼠松果体中 5-HT 总产量和 TPH1 蛋白含量均受到夜间光照的急性抑制。与这些发现一致，TPH1 蛋白的分子分析表明 (a) TPH1 在体外和夜间松果体中的 58 位丝氨酸处被磷酸化；(b) 在这个残基上的 TPH1 磷酸化是 cAMP 增强的 TPH1 蛋白稳定性所必需的。这些数据支持以下模型：松果体中夜间 5-HT 合成增加是由丝氨酸 58 处的 TPH1 磷酸化介导的，这会提高 TPH1 蛋白含量和夜间活性。(b) 在这个残基上的 TPH1 磷酸化是 cAMP 增强的 TPH1 蛋白稳定性所必需的。这些数据支持以下模型：松果体中夜间 5-HT 合成增加是由丝氨酸 58 处的 TPH1 磷酸化介导的，这会提高 TPH1 蛋白含量和夜间活性。(b) 在这个残基上的 TPH1 磷酸化是 cAMP 增强的 TPH1 蛋白稳定性所必需的。这些数据支持以下模型：松果体中夜间 5-HT 合成增加是由丝氨酸 58 处的 TPH1 磷酸化介导的，这会提高 TPH1 蛋白含量和夜间活性。