Tachykinin Signaling Is Required for Induction of the Preovulatory Luteinizing Hormone Surge and Normal Luteinizing Hormone Pulses.
Tachykinin Signaling Is Required for Induction of the Preovulatory Luteinizing Hormone Surge and Normal Luteinizing Hormone Pulses.
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DOI：
10.1159/000509222
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发表时间：
2021
影响因子：
4.1
通讯作者：
Navarro VM
中科院分区：
文献类型：
--
作者：
León S;Fergani C;Talbi R;Maguire CA;Gerutshang A;Seminara SB;Navarro VM
速激肽(NKA、NKB和P物质)是神经内分泌控制生殖的重要组成部分，直接刺激Kiss1神经元控制GnRH的搏动性，对生殖至关重要。尽管速激肽在成功繁殖中起到了这种作用，但Tac1(NKA/SP)和Tac2(NKB)基因敲除的小鼠是可育的，类似于携带NKB信号突变的人类患者的表型，这些患者通常会逆转其性腺功能低下的表型。这表明在不同的速激肽配体-受体系统之间存在补偿机制，以在其中一个系统缺失的情况下维持生殖。为了验证这一假设，我们产生了完全速激肽缺陷小鼠(Tac1/Tac2KO)。雄性小鼠表现出青春期开始延迟，黄体生成素搏动性(黄体生成素脉冲的频率和幅度)降低，但生育能力保持不变。然而，女性在阴道开放后45天内没有表现出青春期开始(第一次发情)的迹象，表现为低频率(但幅度正常)的黄体生成素脉冲，其中80%保持不育。进一步的评估发现，在接受NKB或SP受体拮抗剂治疗的Tac1/Tac2KO女性和WT女性中，完全没有排卵前黄体生成素高峰。这些数据证实了速激肽在青春期开始时间和促黄体生成素搏动性中的基础作用，并揭示了速激肽信号在促进排卵前促黄体生成素高峰中的作用。总体而言，这些发现表明速激肽信号在控制排卵中起主导作用，可能成为改善排卵障碍妇女生殖结局的致病机制和治疗靶点。
Tachykinins (NKA, NKB and Substance P) are important components of the neuroendocrine control of reproduction by directly stimulating Kiss1 neurons to control GnRH pulsatility, essential for reproduction. Despite this role of tachykinins for successful reproduction, knockout mice for Tac1 (NKA/SP) and Tac2 (NKB) genes are fertile, resembling the phenotype of human patients bearing NKB signaling mutations, who often reverse their hypogonadal phenotype. This suggests the existence of compensatory mechanisms among the different tachykinin ligand-receptor systems, to maintain reproduction in the absence of one of them. In order to test this hypothesis, we generated complete tachykinin deficient mice (Tac1/Tac2KO). Male mice displayed delayed puberty onset and decreased LH pulsatility (frequency and amplitude of LH pulses) but preserved fertility. However, females did not show signs of puberty onset (first estrus) within 45 days after vaginal opening, displayed low frequency (but normal amplitude) of LH pulses and 80% of them remained infertile. Further evaluation identified a complete absence of the preovulatory LH surge in Tac1/Tac2KO females as well as in WT females treated with NKB or SP receptor antagonists. These data confirmed a fundamental role for tachykinins in the timing of puberty onset and LH pulsatility and uncovered a role of tachykinin signaling in the facilitation of the preovulatory LH surge. Overall, these findings indicate that tachykinin signaling plays a dominant role in the control of ovulation, with potential implications as pathogenic mechanism and therapeutic target to improve reproductive outcomes in women with ovulation impairments.
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影响因子：
4.8
作者：
Han, Su Young;Cheong, Isaiah;Herbison, Allan E.
通讯作者：
Herbison, Allan E.
影响因子：
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Lippincott, Margaret F.;Leon, Silvia;Seminara, Stephanie Beth
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影响因子：
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通讯作者：
PAYAN, DG
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Herbison, Allan E.
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作者：
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