Melatonin induces the expression of gonadotropin-inhibitory hormone in the avian brain
Melatonin induces the expression of gonadotropin-inhibitory hormone in the avian brain
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DOI：
10.1073/pnas.0403840102
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发表时间：
2005-02-22
影响因子：
11.1
通讯作者：
Tsutsui, K
中科院分区：
文献类型：
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作者：
Ubuka, T;Bentley, GE;Tsutsui, K
我们最近在鹌鹑的下丘脑中发现了一种新的抑制促性腺激素释放的神经肽，并将其命名为促性腺激素抑制激素（GnIH）。含有十二肽GnIH的细胞体和终末分别位于室旁核（PVN）和正中隆起。为了了解GnIH的生理作用，我们研究了调节GnIH表达的机制。在这项研究中，我们表明，褪黑激素来源于松果体和眼睛诱导鹌鹑脑中的GnIH表达。松果体切除术（Px）联合眼眶摘除术（Ex）（Px + Ex）降低间脑（包括PVN和正中隆起）中GnIH前体mRNA的表达和成熟GnIH肽的含量。褪黑激素管理Px加Ex鸟引起剂量依赖性增加的GnIH前体mRNA的表达和成熟肽的生产。GnIH的表达受光周期控制，在短日照下，当褪黑激素分泌持续时间增加时，GnIH的表达增加。为了确定褪黑素对GnIH诱导的作用模式，我们研究了褪黑素受体亚型Mel（1c）在GnIH神经元中的表达。Mel（1c）mRNA的原位杂交结合GnIH免疫细胞化学显示，Mel（1c）mRNA在室旁核的GnIH阳性神经元中表达。褪黑激素受体放射自显影进一步揭示了褪黑激素在PVN中的特异性结合。这些结果表明，褪黑激素是GnIH诱导的关键因素。褪黑激素似乎通过其受体直接作用于GnIH神经元以诱导GnIH表达。据我们所知，这是第一次证明褪黑激素对任何脊椎动物类神经肽诱导的直接作用。
We recently identified a novel hypothalamic neuropeptide inhibiting gonadotropin release in quail and termed it gonadotropin-inhibitory hormone (GnIH). Cell bodies and terminals containing the dodecapeptide GnIH are localized in the paraventricular nucleus (PVN) and median eminence, respectively. To understand the physiological role of GnIH, we investigated the mechanisms that regulate GnIH expression. In this study, we show that melatonin originating from the pineal gland and eyes induces GnIH expression in the quail brain. Pinealectomy (Px) combined with orbital enucleation (Ex) (Px plus Ex) decreased the expression of GnIH precursor mRNA and content of mature GnIH peptide in the diencephalon, which includes the PVN and median eminence. Melatonin administration to Px plus Ex birds caused a dose-dependent increase in expression of GnIH precursor mRNA and production of mature peptide. The expression of GnIH was photoperiodically controlled and increased under short-day photoperiods, when the duration of melatonin secretion increases. To identify the mode of melatonin action on GnIH induction, we investigated the expression of Mel(1c), a melatonin receptor subtype, in GnIH neurons. In situ hybridization of Mel(1c) mRNA combined with immunocytochemistry for GnIH revealed that Mel(1c) mRNA was expressed in GnIH-immunoreactive neurons in the PVN. Melatonin receptor autoradiography further revealed specific binding of melatonin in the PVN. These results indicate that melatonin is a key factor for GnIH induction. Melatonin appears to act directly on GnIH neurons through its receptor to induce GnIH expression. This is the first demonstration, to our knowledge, of a direct action of melatonin on neuropeptide induction in any vertebrate class.