通过尿皮质素2 - CRHR2信号通路抑制雌性小鼠黄体生成素分泌。

IF 3.8 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Richard B McCosh, Helen F Bell, Michael J Kreisman, Katherine Tian, Kellie M Breen
{"title":"通过尿皮质素2 - CRHR2信号通路抑制雌性小鼠黄体生成素分泌。","authors":"Richard B McCosh, Helen F Bell, Michael J Kreisman, Katherine Tian, Kellie M Breen","doi":"10.1210/endocr/bqaf042","DOIUrl":null,"url":null,"abstract":"<p><p>Physiologic stress elicits impairment of reproductive function, in part, by the suppression of luteinizing hormone (LH) secretion. Two populations of kisspeptin-synthesizing neurons in the hypothalamus play essential roles in controlling the pulsatile and surge modes of LH secretion and are potential direct targets of stress-activated neural circuits; however, the mechanism(s) for impairment of kisspeptin cells during stress remain unclear. Here, we conducted 4 experiments to test the hypothesis that corticotropin-releasing hormone receptor 2 (CRHR2) signaling contributes to impaired pulsatile and surge LH secretion via direct actions on kisspeptin cells. First, we observed that cells expressing a specific ligand of CRHR2, urocortin 2 (UCN2), show enhanced c-Fos in the paraventricular nucleus (PVN) following acute hypoglycemia, a metabolic stressor that rapidly suppresses LH pulses by impairing arcuate kisspeptin neuron activation. Second, we determined that central injection of UCN2 rapidly inhibits LH pulses. Furthermore, UCN2 disrupts evening expression of the estradiol-induced LH surge and reduces kisspeptin cell activation in the rostral periventricular hypothalamic region (RP3V). Next, we identified CRHR2 in a majority of both arcuate and RP3V kisspeptin cells. Finally, we observed that UCN2 cells in the PVN are activated following chemogenetic stimulation of catecholamine neurons in the nucleus of the solitary tract. Together these data demonstrate that UCN2-CRHR2 signaling disrupts the pulsatile and surge modes of LH secretion via direct suppression of kisspeptin cells. Furthermore, these findings suggest UCN2 cells in the PVN are regulated by metabolic stress and brainstem norepinephrine signaling pathways that convey stress cues to the hypothalamus.</p>","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932080/pdf/","citationCount":"0","resultStr":"{\"title\":\"Suppression of Luteinizing Hormone Secretion in Female Mice by a Urocortin 2-CRHR2 Signaling Pathway.\",\"authors\":\"Richard B McCosh, Helen F Bell, Michael J Kreisman, Katherine Tian, Kellie M Breen\",\"doi\":\"10.1210/endocr/bqaf042\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Physiologic stress elicits impairment of reproductive function, in part, by the suppression of luteinizing hormone (LH) secretion. Two populations of kisspeptin-synthesizing neurons in the hypothalamus play essential roles in controlling the pulsatile and surge modes of LH secretion and are potential direct targets of stress-activated neural circuits; however, the mechanism(s) for impairment of kisspeptin cells during stress remain unclear. Here, we conducted 4 experiments to test the hypothesis that corticotropin-releasing hormone receptor 2 (CRHR2) signaling contributes to impaired pulsatile and surge LH secretion via direct actions on kisspeptin cells. First, we observed that cells expressing a specific ligand of CRHR2, urocortin 2 (UCN2), show enhanced c-Fos in the paraventricular nucleus (PVN) following acute hypoglycemia, a metabolic stressor that rapidly suppresses LH pulses by impairing arcuate kisspeptin neuron activation. Second, we determined that central injection of UCN2 rapidly inhibits LH pulses. Furthermore, UCN2 disrupts evening expression of the estradiol-induced LH surge and reduces kisspeptin cell activation in the rostral periventricular hypothalamic region (RP3V). Next, we identified CRHR2 in a majority of both arcuate and RP3V kisspeptin cells. Finally, we observed that UCN2 cells in the PVN are activated following chemogenetic stimulation of catecholamine neurons in the nucleus of the solitary tract. Together these data demonstrate that UCN2-CRHR2 signaling disrupts the pulsatile and surge modes of LH secretion via direct suppression of kisspeptin cells. Furthermore, these findings suggest UCN2 cells in the PVN are regulated by metabolic stress and brainstem norepinephrine signaling pathways that convey stress cues to the hypothalamus.</p>\",\"PeriodicalId\":11819,\"journal\":{\"name\":\"Endocrinology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2025-03-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932080/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Endocrinology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1210/endocr/bqaf042\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1210/endocr/bqaf042","RegionNum":3,"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

摘要

生理性应激引起生殖功能的损害,部分原因是由于黄体生成素(LH)的分泌受到抑制。下丘脑中的两种kisspeptin合成神经元在控制LH分泌的脉动和激增模式中发挥重要作用,是应激激活神经回路的潜在直接靶点;然而,应激过程中kisspeptin细胞损伤的机制尚不清楚。在这里,我们进行了四个实验来验证促肾上腺皮质激素释放激素受体2 (CRHR2)信号通过直接作用于kisspeptin细胞而导致脉搏性LH分泌受损和激增的假设。首先,我们观察到,在急性低血糖后,表达CRHR2特异性配体尿皮质素2 (UCN2)的细胞在室旁核(PVN)中显示出增强的c-Fos,这是一种代谢应激源,通过损害弓状kisspeptin神经元的激活来迅速抑制LH脉冲。其次,我们确定中心注射UCN2可以快速抑制LH脉冲。此外,UCN2破坏雌二醇诱导的LH激增的夜间表达,降低吻侧下丘脑室周区(RP3V)的kisspeptin细胞活化。接下来,我们在大多数弓形和RP3V kisspeptin细胞中发现了CRHR2。最后,我们观察到PVN中的UCN2细胞在孤立束核中儿茶酚胺神经元的化学发生刺激后被激活。这些数据表明,UCN2-CRHR2信号通过直接抑制kisspeptin细胞破坏了LH分泌的脉动和激增模式。此外,这些发现表明PVN中的UCN2细胞受代谢应激和脑干去甲肾上腺素信号通路的调节,这些信号通路将应激信号传递给下丘脑。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Suppression of Luteinizing Hormone Secretion in Female Mice by a Urocortin 2-CRHR2 Signaling Pathway.

Physiologic stress elicits impairment of reproductive function, in part, by the suppression of luteinizing hormone (LH) secretion. Two populations of kisspeptin-synthesizing neurons in the hypothalamus play essential roles in controlling the pulsatile and surge modes of LH secretion and are potential direct targets of stress-activated neural circuits; however, the mechanism(s) for impairment of kisspeptin cells during stress remain unclear. Here, we conducted 4 experiments to test the hypothesis that corticotropin-releasing hormone receptor 2 (CRHR2) signaling contributes to impaired pulsatile and surge LH secretion via direct actions on kisspeptin cells. First, we observed that cells expressing a specific ligand of CRHR2, urocortin 2 (UCN2), show enhanced c-Fos in the paraventricular nucleus (PVN) following acute hypoglycemia, a metabolic stressor that rapidly suppresses LH pulses by impairing arcuate kisspeptin neuron activation. Second, we determined that central injection of UCN2 rapidly inhibits LH pulses. Furthermore, UCN2 disrupts evening expression of the estradiol-induced LH surge and reduces kisspeptin cell activation in the rostral periventricular hypothalamic region (RP3V). Next, we identified CRHR2 in a majority of both arcuate and RP3V kisspeptin cells. Finally, we observed that UCN2 cells in the PVN are activated following chemogenetic stimulation of catecholamine neurons in the nucleus of the solitary tract. Together these data demonstrate that UCN2-CRHR2 signaling disrupts the pulsatile and surge modes of LH secretion via direct suppression of kisspeptin cells. Furthermore, these findings suggest UCN2 cells in the PVN are regulated by metabolic stress and brainstem norepinephrine signaling pathways that convey stress cues to the hypothalamus.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Endocrinology
Endocrinology 医学-内分泌学与代谢
CiteScore
8.10
自引率
4.20%
发文量
195
审稿时长
2-3 weeks
期刊介绍: The mission of Endocrinology is to be the authoritative source of emerging hormone science and to disseminate that new knowledge to scientists, clinicians, and the public in a way that will enable "hormone science to health." Endocrinology welcomes the submission of original research investigating endocrine systems and diseases at all levels of biological organization, incorporating molecular mechanistic studies, such as hormone-receptor interactions, in all areas of endocrinology, as well as cross-disciplinary and integrative studies. The editors of Endocrinology encourage the submission of research in emerging areas not traditionally recognized as endocrinology or metabolism in addition to the following traditionally recognized fields: Adrenal; Bone Health and Osteoporosis; Cardiovascular Endocrinology; Diabetes; Endocrine-Disrupting Chemicals; Endocrine Neoplasia and Cancer; Growth; Neuroendocrinology; Nuclear Receptors and Their Ligands; Obesity; Reproductive Endocrinology; Signaling Pathways; and Thyroid.
×
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:481959085
Book学术官方微信