Orphanin FQ/Nociceptin regulates LH release

描述（由申请方提供）：促性腺激素释放激素（GnRH）和随后的促黄体生成激素（LH）释放是生殖神经内分泌控制的最终共同途径。调节GnRH释放的因素知之甚少。最近发现的FQ/伤害感受素（OFQ/N）中的肽E2与几乎所有的GnRH神经元在两种性别中的共表达，以及OFQ/N在体外减少GnRH释放的能力表明OFQ/N在控制GnRH神经元活性中起作用。本文的实验将确定：a）如在下丘脑阻滞中，OFQ/N是否可以抑制体内GnRH/LH释放; B）OFQ/N是否通过其受体阿片样受体-1受体（ORL-1）直接作用于GnRH神经元和/或促性腺激素细胞;和c）OFQ/N是否通过ORL-1直接调节GnRH/LH表达水平。总之，这些研究将提供有关调节GnRH神经元活性和相应LH释放机制的重要信息。

DESCRIPTION (provided by applicant): Gonadotropin-releasing hormone (GnRH) and the subsequent release of luteinizing hormone (LH) is the final common pathway for the neuroendocrine control of reproduction. The factors regulating GnRH release are poorly understood. The recent discovery of the co-expression of the peptide orphanin FQ/nociceptin (OFQ/N) with almost all GnRH neurons in both sexes and in turn the ability of OFQ/N to reduce GnRH release in vitro suggests OFQ/N plays a part in the control of GnRH neuronal activity. The experiments herein will establish: a) if, as in hypothalamic blocks, OFQ/N can inhibit GnRH/LH release in vivo; b) if OFQ/N acts through its receptor, opioid receptor like-1 receptor (ORL-1), to directly effect GnRH neurons and/or gonadotropes; and c) if OFQ/N directly regulates GnRH/LH expression levels through ORL-1. Overall these studies will provide important information about the mechanisms regulating GnRH neuronal activity and the corresponding release of LH.