Orphanin FQ/Nociceptin regulates LH release

描述(申请人提供)：促性腺激素释放激素(GnRH)和随后释放的黄体生成素(LH)是神经内分泌控制生殖的最终共同途径。调节GnRH释放的因素还知之甚少。最近发现孤啡肽FQ/伤害素(OFQ/N)与几乎所有的两性GnRH神经元共表达，进而在体外减少GnRH的释放，这表明OFQ/N在GnRH神经元活动的控制中起一定作用。这里的实验将确定：a)是否像在下丘脑阻断一样，OFQ/N能否在体内抑制GnRH/LH的释放；b)OFQ/N是否通过其受体阿片受体样受体-1(ORL-1)直接作用于GnRH神经元和/或促性腺激素；以及c)OFQ/N是否通过ORL-1直接调节GnRH/LH的表达水平。总体而言，这些研究将提供有关GnRH神经元活动和相应的黄体生成素释放的调节机制的重要信息。

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.