Accumulating evidence suggests that KNDy neurons located in the hypothalamic arcuate nucleus (ARC), which are reported to express kisspeptin, neurokinin B, and dynorphin A, are indispensable for the gonadotropin-releasing hormone (GnRH) pulse generation that results in rhythmic GnRH secretion. The aims of the present study were to investigate the effects of peripheral administration of the neurokinin 3 receptor (NK3R/TACR3, a receptor for neurokinin B) antagonist, SB223412, on GnRH pulse-generating activity and pulsatile luteinizing hormone (LH) secretion in ovariectomized Shiba goats treated with luteal phase levels of estrogen. The NK3R antagonist was infused intravenously for 4 h {0.16 or 1.6 mg/(kg body weight [BW]·4 h)} during which multiple unit activity (MUA) in the ARC was recorded, an electrophysiological technique commonly employed to monitor GnRH pulse generator activity. In a separate experiment, the NK3R antagonist (40 or 200 mg/[kg BW·day]) was administered orally for 7 days to determine whether the NK3R antagonist could modulate pulsatile LH secretion when administered via the oral route. Intravenous infusion of the NK3R antagonist significantly increased the interval of episodic bursts of MUA compared with that of the controls. Oral administration of the antagonist for 7 days also significantly prolonged the interpulse interval of LH pulses. The results of this study demonstrate that peripheral administration of an NK3R antagonist suppresses pulsatile LH secretion by acting on the GnRH pulse generator, suggesting that NK3R antagonist administration could be used to modulate reproductive functions in ruminants.

中文翻译：

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SB223412 的外周给药，一种选择性神经激肽-3 受体拮抗剂，通过作用于雌激素治疗的去卵巢雌性山羊的促性腺激素释放激素脉冲发生器抑制脉动性促黄体激素分泌

越来越多的证据表明，位于下丘脑弓状核 (ARC) 的 KNDy 神经元，据报道表达 Kisspeptin、神经激肽 B 和强啡肽 A，对于促性腺激素释放激素 (GnRH) 脉冲生成是必不可少的，从而导致有节奏的 GnRH 分泌。本研究的目的是研究神经激肽 3 受体（NK3R/TACR3，神经激肽 B 的受体）拮抗剂 SB223412 的外周给药对 GnRH 脉冲生成活性和搏动性黄体生成素 (LH) 分泌的影响。用黄体期雌激素水平治疗的柴山羊。NK3R拮抗剂静脉内输注4小时{0.16或1.6mg/(kg体重[BW]·4小时)}，在此期间记录ARC中的多单位活性(MUA)，一种常用于监测 GnRH 脉冲发生器活动的电生理技术。在单独的实验中，将 NK3R 拮抗剂（40 或 200 毫克/[kg BW·天]）口服给药 7 天，以确定当通过口服途径给药时，NK3R 拮抗剂是否可以调节脉动 LH 分泌。与对照组相比，静脉输注 NK3R 拮抗剂显着增加了 MUA 的间歇性爆发间隔。口服拮抗剂 7 天也显着延长了 LH 脉冲的脉冲间隔。该研究的结果表明，外周施用 NK3R 拮抗剂通过作用于 GnRH 脉冲发生器来抑制脉动性 LH 分泌，表明施用 NK3R 拮抗剂可用于调节反刍动物的生殖功能。