Reduction of arcuate kappa-opioid receptor-expressing cells increased luteinizing hormone pulse frequency in female rats
Reduction of arcuate kappa-opioid receptor-expressing cells increased luteinizing hormone pulse frequency in female rats
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DOI：
10.1507/endocrj.ej20-0832
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发表时间：
2021-01-01
影响因子：
2
通讯作者：
Matsuda, Fuko
中科院分区：
文献类型：
--
作者：
Dai, Mingdao;Nakamura, Sho;Matsuda, Fuko
哺乳动物脉动性分泌促性腺激素释放激素（GnRH）的脑机制对维持生殖功能具有重要意义。越来越多的证据表明，下丘脑弓状核（ARC）中的kisspeptin/neurokinin B/dynorphin A （KNDy）神经元在调节脉动性CinRH和随后的促性腺激素分泌中起关键作用。肌啡肽A （Dyn）及其受体。kappa-阿片受体（KOR，由Oprk1编码）已被证明参与抑制脉动性GnRH/黄体生成素（LH）释放。另一方面，尚不清楚抑制性Dyn信号传导是否影响ARC或其他脑区的KNDy神经元或表达kor的非KNDy细胞。因此，我们旨在阐明ARC特异性Dyn-KOR信号在调节脉动性GnRH/LH释放中的作用，通过使用dyn -偶联皂苷（DynSAP）对表达kor的细胞进行ARC特异性细胞缺失。雌性大鼠切除卵巢后，经雌激素刺激后给予Dyn-SAP。Oprk1的原位杂交显示，Dyn-SAP可显著减少ARC中表达Oprk1的细胞数量，但在下丘脑腹内侧核和室旁核中没有。在服用ARC Dyn-SAP的动物中，1 h脉冲的频率显著增加。在ARC中表达kiss1的细胞数量不受ARC Dyn-SAP处理的影响。ARC内的Dyn-KOR信号似乎介导了GnRH/LH脉冲释放频率的抑制，ARC非kndy型KOR神经元可能参与了GnRH/LH脉冲产生的调节机制。
The brain mechanism responsible for the pulsatile secretion of gonadotropin-releasing hormone (GnRH) is important for maintaining reproductive function in mammals. Accumulating evidence suggests that kisspeptin/neurokinin B/dynorphin A (KNDy) neurons in the hypothalamic arcuate nucleus (ARC) play a critical role in the regulation of pulsatile CinRH and subsequent gonadotropin secretion. Dynorphin A (Dyn) and its receptor. kappa-opioid receptor (KOR, encoded by Oprk1), have been shown to be involved in the suppression of pulsatile GnRH/luteinizing hormone (LH) release. On the other hand, it is still unclear whether the inhibitory Dyn signaling affects KNDy neurons or KOR-expressing non-KNDy cells in the ARC or other brain regions. We therefore aimed to clarify the role of ARC-specific Dyn-KOR signaling in the regulation of pulsatile GnRH/LH release by the ARC specific cell deletion of KOR-expressing cells using Dyn-conjugated-saporin (DynSAP). Estrogen-primed ovariectomized female rats were administered Dyn-SAP to the ARC. In situ hybridization of Oprk1 showed that ARC Dyn-SAP administration significantly decreased the number of Oprk1-expressing cells in the ARC, but not in the ventromedial hypothalamic nucleus and paraventricular nucleus. The frequency of 1.H pulses significantly increased in animals bearing the ARC Dyn-SAP administration. The number of Kiss1-expressing cells in the ARC was not affected by ARC Dyn-SAP treatment. Dyn-KOR signaling within the ARC seems to mediate the suppression of the frequency of pulsatile GnRH/LH release, and ARC non-KNDy KOR neurons may be involved in the mechanism modulating GnRH/LH pulse generation.