Coon Steven L, Del Olmo Elena, Young W Scott, Klein David C
Section on Neuroendocrinology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4480, USA.
J Clin Endocrinol Metab. 2002 Oct;87(10):4699-706. doi: 10.1210/jc.2002-020683.
Arylalkylamine N-acetyltransferase (AANAT; serotonin N-acetyltransferase, EC 2.3.1.87) plays a unique transduction role in vertebrate physiology as the key interface between melatonin production and regulatory mechanisms. Circulating melatonin is elevated at night in all vertebrates, because AANAT activity increases in the pineal gland in response to signals from the circadian clock. Circadian regulation of melatonin synthesis is implicated in a variety of human problems, including jet lag, shift work, insomnia, and abnormal activity rhythms in blind persons. In this report AANAT was studied in the rhesus macaque to better understand human melatonin regulation. AANAT mRNA is abundant in the pineal gland and retina, but not elsewhere; AANAT mRNA is uniformly distributed in the pineal gland, but is limited primarily to the photoreceptor outer segments in the retina. Day and night levels of pineal and retinal AANAT mRNA are similar. In contrast, AANAT activity and protein increase more than 4-fold at night in both tissues. The activity of hydroxyindole-O-methyltransferase, the last enzyme in melatonin synthesis, is tonically high in the pineal gland, but is nearly undetectable in the retina; hydroxyindole O-methyltransferase mRNA levels exhibited a similar pattern. This supports the view that the source of circulating melatonin in primates is the pineal gland. The discovery in this study that rhesus pineal AANAT mRNA is high at all times is of special importance because it shows that posttranscriptional control of this enzyme plays a dominant role in regulating melatonin synthesis.
芳基烷基胺N-乙酰基转移酶（AANAT；血清素N-乙酰基转移酶，EC 2.3.1.87）作为褪黑素生成与调节机制之间的关键界面，在脊椎动物生理学中发挥着独特的转导作用。在所有脊椎动物中，夜间循环中的褪黑素水平都会升高，这是因为松果体中的AANAT活性会响应来自生物钟的信号而增加。褪黑素合成的昼夜节律调节与多种人类问题有关，包括时差反应、轮班工作、失眠以及盲人的异常活动节律。在本报告中，对恒河猴的AANAT进行了研究，以更好地了解人类褪黑素的调节。AANAT mRNA在松果体和视网膜中含量丰富，但在其他部位则不然；AANAT mRNA在松果体中均匀分布，但在视网膜中主要局限于光感受器外段。松果体和视网膜中AANAT mRNA的昼夜水平相似。相比之下，在这两个组织中，夜间AANAT活性和蛋白质增加超过4倍。褪黑素合成的最后一种酶——羟基吲哚-O-甲基转移酶的活性在松果体中持续较高，但在视网膜中几乎检测不到；羟基吲哚O-甲基转移酶的mRNA水平也呈现出类似的模式。这支持了灵长类动物循环褪黑素的来源是松果体这一观点。本研究中发现恒河猴松果体AANAT mRNA始终处于高水平，这一点尤为重要，因为它表明该酶的转录后调控在调节褪黑素合成中起主导作用。
