Orphanin FQ/Nociceptin regulates LH release

描述（由申请人提供）：促性腺激素释放激素（GnRH）和随后释放黄体生成素（LH）是生殖神经内分泌控制的最终共同途径。调节GnRH释放的因素了解甚少。最近发现的肽孤儿肽FQ/nociceptin （OFQ/N）在两性中几乎与所有GnRH神经元共表达，反过来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。本实验将确定：a)如果与下丘脑阻滞一样，OFQ/N可以抑制体内GnRH/LH的释放；b)如果OFQ/N通过其受体，阿片受体样-1受体（ORL-1）起作用，直接影响GnRH神经元和/或促性腺激素；c) OFQ/N是否通过ORL-1直接调控GnRH/LH表达水平。总的来说，这些研究将为GnRH神经元活动的调节机制和相应的LH释放提供重要信息。

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.