Peripheral administration of a κ-opioid receptor agonist nalfurafine inactivates gonadotropin-releasing hormone pulse generator activity in goats

IF 2.5 4区医学 Q3 NEUROSCIENCES Neuroscience Letters Pub Date : 2024-08-10 DOI:10.1016/j.neulet.2024.137918

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Abstract

Neurons co-expressing kisspeptin, neurokinin B, and dynorphin A (KNDy neurons), located in the arcuate nucleus (ARC) of the hypothalamus, are indicated to be the gonadotropin-releasing hormone (GnRH) pulse generator. Dynorphin A is reported to suppress GnRH pulse generator activity. Nalfurafine is a selective agonist of the κ-opioid receptor (KOR), a receptor for dynorphin A, clinically used as an anti-pruritic drug. This study aimed to evaluate the effects of nalfurafine on GnRH pulse generator activity and luteinizing hormone (LH) pulses using female goats. Nalfurafine (0, 2, 4, 8, or 16 μg/head) was intravenously injected into ovariectomized Shiba goats. The multiple unit activity (MUA) in the ARC area was recorded, and plasma LH concentrations were measured 2 and 48 h before and after injection, respectively. The MUA volley interval during 0–2 h after injection was significantly increased in the nalfurafine 8 and 16 μg groups compared with the vehicle group. In 0–2 h after injection, the number of LH pulses was significantly decreased in the nalfurafine 8 and 16 μg groups, and the mean and baseline LH were significantly decreased in all nalfurafine-treated groups (2, 4, 8, and 16 μg) compared with the vehicle group. These results suggest that nalfurafine inhibits the activity of the GnRH pulse generator in the ARC, thus suppressing pulsatile LH secretion. Therefore, nalfurafine could be used as a reproductive inhibitor in mammals.

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外周给药κ-阿片受体激动剂纳呋拉芬可使山羊促性腺激素释放激素脉冲发生器失活。

位于下丘脑弓状核（ARC）的共同表达吻肽、神经激肽 B 和达因啡肽 A 的神经元（KNDy 神经元）被认为是促性腺激素释放激素（GnRH）脉冲发生器。据报道，Dynorphin A 可抑制促性腺激素释放激素脉冲发生器的活动。纳呋拉芬是κ-阿片受体（KOR）的选择性激动剂，而κ-阿片受体是达吗啡 A 的受体，临床上被用作抗瘙痒药物。本研究旨在用雌性山羊评估纳呋拉芬对 GnRH 脉冲发生器活性和促黄体生成素（LH）脉冲的影响。向卵巢切除的芝山羊静脉注射纳呋拉芬（0、2、4、8 或 16 微克/头）。分别在注射前后 2 小时和 48 小时记录 ARC 区域的多单位活动（MUA），并测量血浆 LH 浓度。与车辆组相比，纳呋拉芬 8 和 16 μg 组在注射后 0-2 h 的 MUA 波动间隔显著增加。注射后 0-2 h，纳呋拉芬 8 和 16 μg 组的 LH 脉冲数明显减少，所有纳呋拉芬处理组（2、4、8 和 16 μg）的 LH 平均值和基线值均比对照组明显降低。这些结果表明，纳呋拉芬抑制了 ARC 中 GnRH 脉冲发生器的活性，从而抑制了 LH 的脉冲式分泌。因此，纳呋拉芬可用作哺乳动物的生殖抑制剂。

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来源期刊

Neuroscience Letters 医学-神经科学

CiteScore

5.20

自引率

0.00%

发文量

408

审稿时长

50 days

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