Nociceptin-opioid-related nociceptin receptor 1 signaling partly mediates glucoprivic suppression of luteinizing hormone pulses in female rats: arcuate Kiss1 neurons as a possible target for nociceptin.

IF 3.2 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Marina Takizawa, Koki Yamada, Mayuko Nagae, Shunsuke Seki, Sena Matsuzaki, Masumi Hirabayashi, Naoko Inoue, Yoshihisa Uenoyama, Hiroko Tsukamura
{"title":"Nociceptin-opioid-related nociceptin receptor 1 signaling partly mediates glucoprivic suppression of luteinizing hormone pulses in female rats: arcuate Kiss1 neurons as a possible target for nociceptin.","authors":"Marina Takizawa, Koki Yamada, Mayuko Nagae, Shunsuke Seki, Sena Matsuzaki, Masumi Hirabayashi, Naoko Inoue, Yoshihisa Uenoyama, Hiroko Tsukamura","doi":"10.1159/000546766","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>During malnutrition, mammalian reproductive functions are suppressed by inhibition of the pulsatile release of gonadotropin-releasing hormone (GnRH)/gonadotropins. This study aimed to investigate whether nociceptin-opioid-related nociceptin receptor 1 (OPRL1) signaling mediates glucoprivic suppression of luteinizing hormone (LH) pulses in female rats.</p><p><strong>Methods and results: </strong>RNA sequencing analysis of tdTomato-positive arcuate (ARC) kisspeptin neurons obtained from Kiss1 (kisspeptin gene)-Cre/Cre-dependent tdTomato reporter female rats showed that Oprl1 mRNA expression was evident in ARC kisspeptin neurons. Double in situ hybridization for Kiss1 and Oprl1 or prepronociceptin gene (Pnoc) revealed that approximately 20% of Kiss1-expressing cells co-expressed Oprl1, but not Pnoc in ovariectomized (OVX) wild-type rats treated with diestrus levels of estradiol-17β (low E2). Administration of [N-Phe1]-orphanin FQ (1-13) amide (NC13), a selective OPRL1 antagonist, to the third ventricle (3V) transiently reversed the suppression of LH pulses induced by intravenous (iv) 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, in OVX + low E2 rats. The frequency of LH pulses during the first hour of the 3-h sampling period were significantly higher in 3V NC13-treated rats than in vehicle-treated controls. In contrast, 3V NC13 administration failed to affect LH pulses in OVX + low E2 rats without iv 2DG treatment. Furthermore, iv 2DG treatment significantly increased the percentage of fos-positive ARC Pnoc-expressing cells in OVX + low E2 rats.</p><p><strong>Conclusion: </strong>These results indicate that ARC nociceptin-OPRL1 signaling partly mediates the glucoprivic suppression of LH pulses, and that nociceptin may directly suppress ARC kisspeptin neurons, the GnRH/LH pulse generator in female rats.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-19"},"PeriodicalIF":3.2000,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroendocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000546766","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: During malnutrition, mammalian reproductive functions are suppressed by inhibition of the pulsatile release of gonadotropin-releasing hormone (GnRH)/gonadotropins. This study aimed to investigate whether nociceptin-opioid-related nociceptin receptor 1 (OPRL1) signaling mediates glucoprivic suppression of luteinizing hormone (LH) pulses in female rats.

Methods and results: RNA sequencing analysis of tdTomato-positive arcuate (ARC) kisspeptin neurons obtained from Kiss1 (kisspeptin gene)-Cre/Cre-dependent tdTomato reporter female rats showed that Oprl1 mRNA expression was evident in ARC kisspeptin neurons. Double in situ hybridization for Kiss1 and Oprl1 or prepronociceptin gene (Pnoc) revealed that approximately 20% of Kiss1-expressing cells co-expressed Oprl1, but not Pnoc in ovariectomized (OVX) wild-type rats treated with diestrus levels of estradiol-17β (low E2). Administration of [N-Phe1]-orphanin FQ (1-13) amide (NC13), a selective OPRL1 antagonist, to the third ventricle (3V) transiently reversed the suppression of LH pulses induced by intravenous (iv) 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, in OVX + low E2 rats. The frequency of LH pulses during the first hour of the 3-h sampling period were significantly higher in 3V NC13-treated rats than in vehicle-treated controls. In contrast, 3V NC13 administration failed to affect LH pulses in OVX + low E2 rats without iv 2DG treatment. Furthermore, iv 2DG treatment significantly increased the percentage of fos-positive ARC Pnoc-expressing cells in OVX + low E2 rats.

Conclusion: These results indicate that ARC nociceptin-OPRL1 signaling partly mediates the glucoprivic suppression of LH pulses, and that nociceptin may directly suppress ARC kisspeptin neurons, the GnRH/LH pulse generator in female rats.

痛觉肽-阿片类药物相关痛觉肽受体1信号部分介导雌性大鼠葡萄糖促黄体生成素脉冲的抑制:弓形吻s1神经元可能是痛觉肽的靶点。
在营养不良期间,哺乳动物的生殖功能通过抑制促性腺激素释放激素(GnRH)/促性腺激素的脉动释放而受到抑制。本研究旨在探讨痛觉肽-阿片类药物相关痛觉肽受体1 (OPRL1)信号是否介导雌性大鼠黄体生成素(LH)脉冲的葡萄糖抑制。方法和结果:对kisspeptin基因-Cre/ cre依赖的tdTomato报告雌性大鼠获得的tdTomato-positive arcuate (ARC) kisspeptin神经元进行RNA测序分析,发现在ARC kisspeptin神经元中有明显的Oprl1 mRNA表达。对Kiss1和Oprl1或proproceeptin基因(Pnoc)的双原位杂交发现,在去卵巢(OVX)野生型大鼠中,约20%的Kiss1表达细胞共表达Oprl1,但不表达Pnoc。在OVX +低E2大鼠中,将选择性OPRL1拮抗剂[N-Phe1]-孤啡肽FQ(1-13)酰胺(NC13)给予第三心室(3V)可短暂逆转静脉注射(iv) 2-脱氧-d -葡萄糖(2DG)(葡萄糖利用抑制剂)诱导的LH脉冲抑制。3V nc13处理的大鼠在3小时采样周期的第一个小时内LH脉冲频率显著高于对照。相比之下,3V NC13给药没有影响OVX +低E2大鼠的LH脉冲。此外,iv 2DG处理显著增加OVX +低E2大鼠fos阳性ARC pnoc表达细胞的百分比。结论:上述结果提示ARC nociceptin- oprl1信号通路在一定程度上介导了孕激素对LH脉冲的抑制,而nociceptin可能直接抑制雌性大鼠GnRH/LH脉冲产生器ARC kisspeptin神经元。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Neuroendocrinology
Neuroendocrinology 医学-内分泌学与代谢
CiteScore
8.30
自引率
2.40%
发文量
50
审稿时长
6-12 weeks
期刊介绍: ''Neuroendocrinology'' publishes papers reporting original research in basic and clinical neuroendocrinology. The journal explores the complex interactions between neuronal networks and endocrine glands (in some instances also immunecells) in both central and peripheral nervous systems. Original contributions cover all aspects of the field, from molecular and cellular neuroendocrinology, physiology, pharmacology, and the neuroanatomy of neuroendocrine systems to neuroendocrine correlates of behaviour, clinical neuroendocrinology and neuroendocrine cancers. Readers also benefit from reviews by noted experts, which highlight especially active areas of current research, and special focus editions of topical interest.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信