Chemogenetic Activation of RFRP Neurons Reduces LH Pulse Frequency in Female but not Male Mice.

IF 3 Q2 ENDOCRINOLOGY & METABOLISM
Journal of the Endocrine Society Pub Date : 2024-09-17 eCollection Date: 2024-09-26 DOI:10.1210/jendso/bvae159
India L Sawyer, Maggie C Evans, Asha Mamgain, Caroline Decourt, Karl J Iremonger, Greg M Anderson
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引用次数: 0

Abstract

Context: The neuropeptide RFRP-3 (RFamide-related peptide-3) is thought to play a role in the negative regulation of fertility. However, the exogenous administration of RFRP-3 yields varying results depending on the dose and route of administration, sex of the subject, and many other variables. Manipulation of in vivo neuronal activity using DREADDs (designer receptor exclusively activated by designer drugs) technology enables investigation of cell type-specific neuronal activation in a manner that better reflects endogenous neuronal activity.

Objective: To test the effects of RFRP neuronal activation on pulsatile luteinizing hormone (LH) secretion.

Methods: We generated mice expressing the stimulatory hM3Dq designer receptor exclusively in RFRP cells using 2 different Cre-loxP-mediated approaches: (1) we bred mice to express hM3Dq in all Rfrp-Cre-expressing cells, including some that transiently expressed Rfrp-Cre neonatally (RFRP × hM3Dq mice), and (2) we stereotaxically injected Cre-dependent hM3Dq into the dorsomedial nucleus of RFRP-Cre mice to drive hM3Dq expression exclusively in a subpopulation of adult Rfrp-Cre neurons (RFRP-AAV-hM3Dq mice). We then investigated the effects of acute hM3Dq activation on LH pulse frequency in RFRP × hM3Dq mice, RFRP-AAV-hM3Dq mice, and their respective controls.

Results: In both female RFRP × hM3Dq and RFRP-AAV-hM3Dq mice, chemogenetic activation of Cre-driven hM3Dq led to a significant 35% to 50% reduction in LH pulse frequency compared with controls, while no differences in pulse amplitude or mean LH concentration were observed. In marked contrast, RFRP activation did not cause any changes to LH pulse dynamics in male mice.

Conclusions: These data show for the first time that activation of neurons that have expressed Rfrp, or of a subset of adult RFRP neurons, can independently suppress LH pulsatility in female, but not male mice.

化学基因激活 RFRP 神经元可降低雌性小鼠的 LH 脉冲频率,而非雄性小鼠。
背景:神经肽 RFRP-3(RFamide-related peptide-3,射频酰胺相关肽-3)被认为在生育力的负向调节中发挥作用。然而,外源性施用 RFRP-3 会产生不同的结果,这取决于施用的剂量和途径、受试者的性别以及许多其他变量。利用 DREADDs(专门由设计药物激活的设计受体)技术操纵体内神经元活动,能以更好地反映内源性神经元活动的方式研究细胞类型特异性神经元激活:目的:测试 RFRP 神经元激活对黄体生成素(LH)脉冲式分泌的影响:方法:我们利用两种不同的 Cre-loxP 介导方法,在 RFRP 细胞中产生了专门表达刺激性 hM3Dq 设计者受体的小鼠:(1)我们培育了在所有 Rfrp-Cre 表达细胞中表达 hM3Dq 的小鼠,包括一些在新生儿期瞬时表达 Rfrp-Cre 的小鼠(RFRP × hM3Dq 小鼠);(2)我们将 Cre 依赖性 hM3Dq 立体定向注射到 RFRP-Cre 小鼠的背内侧核中,以驱动 hM3Dq 在成年 Rfrp-Cre 神经元亚群中独家表达(RFRP-AAV-hM3Dq 小鼠)。然后,我们研究了急性 hM3Dq 激活对 RFRP × hM3Dq 小鼠、RFRP-AAV-hM3Dq 小鼠及其各自对照组 LH 脉冲频率的影响:结果:在雌性RFRP × hM3Dq小鼠和RFRP-AAV-hM3Dq小鼠中,与对照组相比,Cre驱动的hM3Dq的化学激活导致LH脉冲频率显著降低35%至50%,而在脉冲幅度或平均LH浓度方面没有观察到差异。与此形成鲜明对比的是,RFRP激活并没有导致雄性小鼠LH脉冲动态发生任何变化:这些数据首次表明,激活表达了Rfrp的神经元或成年RFRP神经元亚群可独立抑制雌性而非雄性小鼠的LH脉动性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of the Endocrine Society
Journal of the Endocrine Society Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
5.50
自引率
0.00%
发文量
2039
审稿时长
9 weeks
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