Involvement of nociceptin/orphanin FQ in release of hypothalamic GnRH mediated by ORL1 receptor in ovariectomized rats

Abstract

Aim: To investigate effect of the nociceptin/orphanin FQ (OFQ) on hypothalamus gonadotropin‐releasing hormone (GnRH) release in ovariectomized (OVX) rats. Methods: GnRH radioimmunoassay (RIA) was used to study the effect of OFQ on GnRH release in hypothalamus slices in vitro. Push‐pull perfusion and intracerebroventicular (icv) injection were used to examine the effect of OFQ on GnRH release in the hypothalamus medial preoptic area (POA) in vivo. Ovariectomies were performed on female Sprague‐Dawley rats, and their plasma luteinizing hormone (LH) levels were measured after icv injection of OFQ with or without [Nphe1]NC(l‐13)NH2,a competitive antagonist of opioid receptor‐like 1 receptor (ORL1 receptor). Reverse transcription‐polymerase chain reaction (RT‐PCR) was used to investigate the expression of the ORL1 receptor in rat pituitary. Results: GnRH release from hypothalamus slices was inhibited 90 min after the administration of 2 mmol/L and 20 mmol/L OFQ (P<0.05). Accordingly, GnRH release from hypothalamus POA was also significantly reduced by the injection of 0.2 mmol/L and 2 mmol/L OFQ. Plasma LH levels were also decreased significantly 2h after icv injection of 20 nmol OFQ in OVX rats (P<0.05) and this effect could be abolished by pretreatment with 20 nmol [Nphe1]NC(1‐13)NH2, that is, NC13. More interestingly, plasma LH levels in OVX rats increased markedly 2 h after icv injection of 100 nmol and 200 nmol NC13. RT‐PCR analysis further revealed that the ORL1 receptor was not expressed in the pituitary of OVX rats. Conclusion: Central administration of nociceptin/orphanin FQ might inhibit the release of hypothalamic GnRH and decrease the plasma LH levels through ORL1 receptors in OVX rats.

Role of hypothalamus nociceptin/orphanin FQ in pre-ovulatory luteinizing hormone surge of estrogen and progesterone-primed, ovariectomized rats

“…These studies offer important clues about a possible participation of OFQ in the regulation of the HPOA. Our initial experiments confirmed that OFQ icv injections of 20 or 200 nmol can significantly decrease plasma LH levels of OVX rats, and the strongest effects occurred 2 h after administration [8] . Based on the results, we hypothesize that OFQ is most likely a predominant regulator of GnRH and LH secretion, at least in rats.…”

“…The homology between the opiate peptides and OFQ, as well as between their receptors, coupled with the localization of OFQ and its receptor in the hypothalamus, suggest a neuroendocrine role for OFQ in reproduction [13,21] . Previous studies have shown that OFQ can potently inhibit GnRH release from MBH fragments in vitro and from the POA of OVX rats in vivo [7,8] . These studies offer important clues about a possible participation of OFQ in the regulation of the HPOA.…”

“…A recent study has revealed that OFQ potently and dose-dependently inhibits forskolin-induced, gonadotropin-releasing hormone (GnRH) release from rat hypotha-lamic fragments [7] . Our previous work demonstrates that the central administration of OFQ might inhibit the release of hypothalamic GnRH and decrease the level of plasma luteinizing hormone (LH) via the ORL1 receptor in ovariectomized (OVX) rats [8] . Such an OFQ-induced alteration of anterior pituitary hormone secretion would implicate OFQ as an important modulator of reproductive function.…”

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

“…Previous studies have shown OFQ can potently inhibit GnRH release from medial basal hypothalamic (MBH) fragments in vitro [6] . Recent data from our laboratory showed central administration of OFQ could inhibit the release of GnRH in hypothalamus mPOA of anesthetized OVX rats [9] . To aviod the possible impact of anesthesia on hypothalamic neuroendocrinologic secretion, the freely moving concious OVX rats were adopted in this study.…”

“…OFQ can inhibit LH pulse frequency and suppress LH pulse amplitude in both luteal phase and ovariectomized ewes [8] . Similarly, our previous studies demonstrated that central administration of OFQ might inhibit the release of GnRH in hypothalamus medial preoptic area (mPOA) and decrease the level of plasma luteinizing hormone (LH) in anesthetized ovariectomized (OVX) rats [9] . Since GnRH is synthesized in neuronal cell bodies diffusely distributed across the basal forebrain and is secreted from neuronal terminals in the median eminence (ME) [10] , ME is regarded as the ultimate pathway in the network regulation of GnRH release by several neurotransmitters and neuropeptides.…”