NK3R signalling in the posterodorsal medial amygdala is involved in stress-induced suppression of pulsatile LH secretion in female mice

IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM Journal of Neuroendocrinology Pub Date : 2024-03-22 DOI:10.1111/jne.13384
Deyana Ivanova, Margaritis Voliotis, Krasimira Tsaneva-Atanasova, Kevin T. O'Byrne, Xiao-Feng Li
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Abstract

Psychosocial stress negatively impacts reproductive function by inhibiting pulsatile luteinizing hormone (LH) secretion. The posterodorsal medial amygdala (MePD) is responsible in part for processing stress and modulating the reproductive axis. Activation of the neurokinin 3 receptor (NK3R) suppresses the gonadotropin-releasing hormone (GnRH) pulse generator, under hypoestrogenic conditions, and NK3R activity in the amygdala has been documented to play a role in stress and anxiety. We investigate whether NK3R activation in the MePD is involved in mediating the inhibitory effect of psychosocial stress on LH pulsatility in ovariectomised female mice. First, we administered senktide, an NK3R agonist, into the MePD and monitored the effect on pulsatile LH secretion. We then delivered SB222200, a selective NK3R antagonist, intra-MePD in the presence of predator odour, 2,4,5-trimethylthiazole (TMT) and examined the effect on LH pulses. Senktide administration into the MePD dose-dependently suppresses pulsatile LH secretion. Moreover, NK3R signalling in the MePD mediates TMT-induced suppression of the GnRH pulse generator, which we verified using a mathematical model. The model verifies our experimental findings: (i) predator odour exposure inhibits LH pulses, (ii) activation of NK3R in the MePD inhibits LH pulses and (iii) NK3R antagonism in the MePD blocks stressor-induced inhibition of LH pulse frequency in the absence of ovarian steroids. These results demonstrate for the first time that NK3R neurons in the MePD mediate psychosocial stress-induced suppression of the GnRH pulse generator.

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雌性小鼠后背内侧杏仁核中的 NK3R 信号参与了压力诱导的脉冲性 LH 分泌抑制。
社会心理压力会抑制黄体生成素(LH)的搏动性分泌,从而对生殖功能产生负面影响。后背内侧杏仁核(MePD)部分负责处理压力和调节生殖轴。在低雌激素条件下,神经激肽 3 受体(NK3R)的激活可抑制促性腺激素释放激素(GnRH)脉冲发生器,杏仁核中的 NK3R 活性已被证实在压力和焦虑中发挥作用。我们研究了MePD中的NK3R激活是否参与介导了社会心理应激对卵巢切除雌性小鼠LH脉动性的抑制作用。首先,我们将 NK3R 激动剂 Senktide 注入 MePD,并监测其对 LH 脉动分泌的影响。然后,我们在捕食者气味、2,4,5-三甲基噻唑(TMT)存在的情况下,在MePD内注射选择性NK3R拮抗剂SB222200,并检测其对LH脉冲的影响。在MePD内注射森克特肽可剂量依赖性地抑制LH脉冲分泌。此外,MePD中的NK3R信号介导了TMT对GnRH脉冲发生器的抑制,我们用数学模型验证了这一点。该模型验证了我们的实验结果:(i)捕食者气味暴露会抑制 LH 脉冲;(ii)MePD 中的 NK3R 激活会抑制 LH 脉冲;(iii)MePD 中的 NK3R 拮抗会在没有卵巢类固醇的情况下阻止压力源对 LH 脉冲频率的抑制。这些结果首次证明,MePD中的NK3R神经元介导了社会心理压力对GnRH脉冲发生器的抑制。
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来源期刊
Journal of Neuroendocrinology
Journal of Neuroendocrinology 医学-内分泌学与代谢
CiteScore
6.40
自引率
6.20%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Journal of Neuroendocrinology provides the principal international focus for the newest ideas in classical neuroendocrinology and its expanding interface with the regulation of behavioural, cognitive, developmental, degenerative and metabolic processes. Through the rapid publication of original manuscripts and provocative review articles, it provides essential reading for basic scientists and clinicians researching in this rapidly expanding field. In determining content, the primary considerations are excellence, relevance and novelty. While Journal of Neuroendocrinology reflects the broad scientific and clinical interests of the BSN membership, the editorial team, led by Professor Julian Mercer, ensures that the journal’s ethos, authorship, content and purpose are those expected of a leading international publication.
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