Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Biomed Res Int. 2013;2013:546516. doi: 10.1155/2013/546516. Epub 2013 Jul 1.
Pineal melatonin synthesis can be modulated by many peptides, including insulin. Because melatonin appears to alter leptin synthesis, in this work we aimed to investigate whether leptin would have a role on norepinephrine- (NE-)mediated melatonin synthesis in cultured rat pineal glands. According to our data, cultured rat pineal glands express leptin receptor isoform b (Ob-Rb). Pineal expression of Ob-Rb mRNA was also observed in vivo. Administration of leptin (1 nM) associated with NE ( 1 µM) reduced melatonin content as well as arylalkylamine-N-acetyl transferase (AANAT) activity and expression in cultured pineal glands. Leptin treatment per se induced the expression of STAT3 in cultured pineal glands, but STAT3 does not participate in the leptin modulation of NE-mediated pineal melatonin synthesis. In addition, the expression of inducible cAMP early repressor (ICER) was further induced by leptin challenge when associated with NE. In conclusion, leptin inhibition of pineal melatonin synthesis appears to be mediated by a reduction in AANAT activity and expression as well as by increased expression of Icer mRNA. Peptidergic signaling within the pineal gland appears to be one of the most important signals which modulates melatonin synthesis; leptin, as a member of this system, is not an exception.
松果体褪黑素的合成可以被许多肽类物质所调节，包括胰岛素。由于褪黑素似乎可以改变瘦素的合成，在这项工作中，我们旨在研究瘦素是否会对去甲肾上腺素（NE）介导的培养大鼠松果体褪黑素合成产生影响。根据我们的数据，培养的大鼠松果体表达瘦素受体亚型 b（Ob-Rb）。体内也观察到松果体 Ob-Rb mRNA 的表达。瘦素（1 nM）与 NE（1 µM）联合给药可减少培养的松果体中褪黑素的含量以及芳香族烷基胺-N-乙酰转移酶（AANAT）的活性和表达。瘦素处理本身可诱导培养的松果体中 STAT3 的表达，但 STAT3 不参与瘦素对 NE 介导的松果体褪黑素合成的调节。此外，当与 NE 联合使用时，瘦素还可进一步诱导诱导型 cAMP 早期应答元件（ICER）的表达。总之，瘦素抑制松果体褪黑素的合成似乎是通过降低 AANAT 的活性和表达以及增加 Icer mRNA 的表达来实现的。松果体内的肽信号似乎是调节褪黑素合成的最重要信号之一；瘦素作为该系统的一员，也不例外。
