Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Avda. Manuel Siurot S/N, 41013, Seville, Spain; Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Universidad de Sevilla, Avda. Sanchez Pizjuan S/N, 41009, Seville, Spain.
Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Avda. Manuel Siurot S/N, 41013, Seville, Spain.
Mol Metab. 2019 Oct;28:83-90. doi: 10.1016/j.molmet.2019.07.007. Epub 2019 Jul 24.
To obtain greater knowledge of the extra-pineal sources of melatonin during development, the amount of indolamine and the expression levels of the last two enzymes involved in its biosynthesis, Arylalkylamine N-acetyltransferase (AANAT) and acetylserotonin O-methyltransferase (ASMT), were analyzed in the human thymus from children from three different age groups (from days to years). The melatonin membrane and nuclear receptor expression levels also were studied.
Quantitative reverse transcriptase PCR and western blot were performed to investigate the receptor and enzyme expression levels. The results were examined and correlated with the ages of the thymuses.
We found high levels of indolamine in the thymuses of newborns (younger than 1 month), which decreased during development; thymuses from the months (from 2 to 11 months) and years (from 1 to 12 years) groups showed lower levels. A similar decline was also observed in the mRNA of the AANAT enzyme and the expression levels of melatonin receptors. However, ASMT expression was exactly the opposite, with low levels in the newborn group and higher levels in the years group. Our results show that the thymic synthesis of melatonin occurs very early in childhood. Additionally, this is the first report that is focused on melatonin receptors expression in the human thymus.
Considering the limited melatonin synthesis performed by the newborn pineal gland, we suggest that the high levels of melatonin found in human thymus in this experimental group arise from synthesis in the tissue itself, which could be contributing to the immune efficiency at the thymic level.
为了更深入地了解褪黑素在发育过程中的松果体外来源,我们分析了来自三个不同年龄组(从几天到几年)的儿童胸腺中的吲哚胺含量以及最后两种参与其生物合成的酶(芳香族烷基胺 N-乙酰转移酶(AANAT)和乙酰血清素 O-甲基转移酶(ASMT))的表达水平。同时,我们还研究了褪黑素膜和核受体的表达水平。
采用定量逆转录 PCR 和 Western blot 法检测受体和酶的表达水平。并对结果进行了检查,并与胸腺的年龄进行了相关性分析。
我们发现,新生儿(1 个月以下)胸腺中的吲哚胺含量较高,随着发育过程而降低;2-11 个月和 1-12 岁组的胸腺含量较低。AANAT 酶的 mRNA 和褪黑素受体的表达水平也观察到类似的下降。然而,ASMT 的表达情况正好相反,新生儿组含量较低,而 12 岁组含量较高。我们的结果表明,褪黑素在儿童早期就已经在胸腺中合成。此外,这是首次专注于褪黑素受体在人胸腺中表达的研究。
考虑到新生儿松果腺合成的褪黑素有限,我们认为在该实验组中,在人胸腺中发现的高水平褪黑素可能来自组织本身的合成,这可能有助于在胸腺水平上提高免疫效率。