Central administration of Orphanin FQ inhibits GnRH secretion by ORL1 receptor in the median eminence of freely moving ovariectomized rats

Neurosci Bull. 2009 Feb;25(1):1-6. doi: 10.1007/s12264-009-1119-5.

Abstract

Objective: This study aimed to investigate the possible role of Orphanin FQ (OFQ) in the regulation of hypo-thalamic gonadotropin-releasing hormone (GnRH) secretion.

Methods: The method of push-pull perfusion and radioimmuno-assay (RIA) were adopted to examine the secretory profile of GnRH in the median eminence (ME) in freely moving ovari-ectomized (OVX) rats after intracerebroventricular (icv) injection of OFQ and/or [Nphe(1)]NC(1-13)NH(2) (NC13), a competitive antagonists of the opioid receptor-like 1 receptor (ORL1 receptor).

Results: GnRH release from ME significantly decreased from 40 min to 80 min after the administration of 20 and 200 nmol OFQ in OVX rats (P < 0.05). This inhibitory effect of 20 nmol OFQ could be abolished by pretreatment with equal dose of NC13. More interestingly, GnRH secretion from ME was increased markedly 60 min after icv injection of 100 and 200 nmol NC13 (P < 0.05).

Conclusion: Our results suggested central administration of OFQ could inhibit the release of GnRH in the ME of hypothalamus through ORL1 receptor, providing further in vivo evidence supporting the role of OFQ in the control of GnRH secretion.

目的: 本文旨在研究孤啡肽 (Orphanin FQ, OFQ) 对下丘脑促性腺激素释放激素 (gonadotropin-releasing hormone, GnRH) 释放的调节机制。

方法: 应用推挽灌流和放射性免疫测定方法观察侧脑室注射OFQ和/或孤儿受体 (opioid receptor-like1 receptor, ORL1 receptor) 特异性拮抗剂NC13对清醒去卵巢 (ovariectomized, OVX)大鼠下丘脑正中隆起 (median eminence, ME) GnRH 释放的影响。

结果: 侧脑室给予20 和200 nmol孤啡肽, 注射后40 到80 min 可明显抑 制OVX大鼠ME的GnRH释放 (P < 0.05), 该作用可被侧脑室注射等剂量NC13预处理所阻断。 侧脑室单独给予100 和200 nmol NC13, 注射后60 min 可使OVX大鼠ME的GnRH释放显著增加 (P < 0.05)。

结论: 中枢注射OFQ通过 ORL1 受体可抑制OVX大鼠ME的GnRH释放, 提示下丘脑OFQ可能参与了GnRH释放的生理调节机制。

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Dose-Response Relationship, Drug
  • Female
  • Gonadotropin-Releasing Hormone / metabolism*
  • Median Eminence / metabolism*
  • Narcotic Antagonists
  • Nociceptin
  • Nociceptin Receptor
  • Opioid Peptides / pharmacology*
  • Ovariectomy / methods
  • Peptide Fragments / pharmacology
  • Radioimmunoassay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid / metabolism*
  • Secretory Pathway / drug effects*
  • Vasodilator Agents / pharmacology*
  • Wakefulness / physiology*

Substances

  • Narcotic Antagonists
  • Opioid Peptides
  • Peptide Fragments
  • Receptors, Opioid
  • Vasodilator Agents
  • nociceptin-(1-13)-NH2, NPhe(1)-
  • Gonadotropin-Releasing Hormone
  • Nociceptin Receptor
  • Oprl protein, rat