It is well-established that the hypothalamic-pituitary-gonadal (HPG) axis is suppressed due to negative energy balance. However, less information is available on whether kisspeptin neuronal activity contributes to fasting-induced responses. In the present study, female and male mice were fasted for 24 hours or provided food ad libitum (fed group) to determine whether acute fasting is sufficient to modulate kisspeptin neuronal activity. In female mice, fasting attenuated luteinizing hormone (LH) and prolactin (PRL) serum levels and increased follicle-stimulating hormone levels compared with the fed group. In contrast, fasting did not affect gonadotropin or PRL secretion in male mice. By measuring genes related to LH pulse generation in micropunches obtained from the arcuate nucleus of the hypothalamus (ARH), we observed that fasting reduced Kiss1 mRNA levels in female and male mice. In contrast, Pdyn expression was upregulated only in fasted female mice, whereas no changes in the Tac2 mRNA levels were observed in both sexes. Interestingly, the frequency and amplitude of the GABAergic postsynaptic currents recorded from ARH kisspeptin neurons (ARHKisspeptin) were reduced in 24-hour fasted female mice but not in males. Additionally, neuropeptide Y induced a hyperpolarization in the resting membrane potential of ARHKisspeptin neurons of fed female mice but not in males. Thus, the response of ARHKisspeptin neurons to fasting is sexually dependent with a female bias, associated with changes in gonadotropins and PRL secretion. Our findings suggest that GABAergic transmission to ARHKisspeptin neurons modulates the activity of the HPG axis during situations of negative energy balance.

中文翻译：

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禁食调节雌性小鼠中 GABA 能突触传递至弓形 Kisspeptin 神经元。

众所周知，下丘脑-垂体-性腺（HPG）轴由于能量负平衡而受到抑制。然而，关于 Kisspeptin 神经元活动是否有助于禁食引起的反应的信息较少。在本研究中，雌性和雄性小鼠禁食 24 小时或随意提供食物（喂食组），以确定急性禁食是否足以调节 Kisspeptin 神经元活性。在雌性小鼠中，与进食组相比，禁食会降低黄体生成素（LH）和催乳素（PRL）血清水平，并增加促卵泡激素水平。相比之下，禁食并不影响雄性小鼠的促性腺激素或催乳素分泌。通过测量从下丘脑弓状核 (ARH) 获得的微孔中与 LH 脉冲产生相关的基因，我们观察到禁食降低了雌性和雄性小鼠的 Kiss1 mRNA 水平。相比之下，Pdyn 表达仅在禁食的雌性小鼠中上调，而在两性中均未观察到 Tac2 mRNA 水平的变化。有趣的是，在 24 小时禁食的雌性小鼠中，ARH Kisspeptin 神经元 (ARHKisspeptin) 记录的 GABA 能突触后电流的频率和幅度有所降低，但在雄性小鼠中则没有。此外，神经肽 Y 会诱导喂食雌性小鼠的 ARHKisspeptin 神经元的静息膜电位超极化，但雄性小鼠不会。因此，ARHKisspeptin 神经元对禁食的反应具有性别依赖性，且女性偏向，与促性腺激素和 PRL 分泌的变化相关。我们的研究结果表明，在能量负平衡的情况下，GABA 能传输到 ARHKisspeptin 神经元可调节 HPG 轴的活动。