The progesterone metabolite, allopregnanolone (AlloP), is a GABAA receptor modulating steroid and is known to have orexigenic and pro-obesity effects. The neurobiological mechanisms underpinning these effects are most likely due to enhanced GABAergic signaling in the lateral arcuate nucleus (ARC) and medial paraventricular nucleus (PVN) of the hypothalamus. Inspired by the finding that GABAergic signaling is also important for the orexigenic effects of the circulating hormone, ghrelin, we sought to determine the extent to which AlloP (one of the most potent endogenous GABAA-receptor modulators) operates alongside ghrelin to enhance food intake. Male rats with ad libitum access to standard chow were injected intravenously with AlloP and/or ghrelin, alone or in combination. The intake of the standard chow was greater after AlloP 1 mg/kg together with ghrelin 30 μg/kg than with 30 μg/kg ghrelin alone. Food intake was also increased for the combined treatment of AlloP 0.5 mg/kg + ghrelin 10 μg/kg, AlloP 1 mg/kg + ghrelin 10 μg/kg, and AlloP 0.5 mg/kg + ghrelin 30 μg/kg. There was no significant difference in food intake between the two ghrelin doses or between the two doses of AlloP and the vehicle. In electrophysiological studies, physiologically relevant concentrations of AlloP prolonged the current decay time of spontaneous inhibitory post-synaptic current of dissociated cells of the ARC and PVN. We conclude that AlloP enhances the hyperphagic effect of ghrelin, findings of potential relevance for the hyperphagia associated with the luteal phase of the reproductive cycle.

中文翻译：

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别孕酮对大鼠胃饥饿素促食欲作用的累加作用

孕酮代谢物别孕酮 (AlloP) 是一种 GABAA 受体调节类固醇，已知具有促食欲和促肥胖作用。支持这些效应的神经生物学机制很可能是由于下丘脑外侧弓状核 (ARC) 和内侧室旁核 (PVN) 中 GABA 能信号增强。受 GABA 能信号对循环激素 ghrelin 的促食欲作用也很重要这一发现的启发，我们试图确定 AlloP（最有效的内源性 GABAA 受体调节剂之一）与生长激素释放肽一起作用以增加食物摄入的程度。可随意获取标准食物的雄性大鼠单独或联合静脉注射 AlloP 和/或生长素释放肽。AlloP 1 mg/kg 和 ghrelin 30 μg/kg 后标准食物的摄入量大于单独 30 μg/kg ghrelin 的摄入量。AlloP 0.5 mg/kg + ghrelin 10 μg/kg、AlloP 1 mg/kg + ghrelin 10 μg/kg和AlloP 0.5 mg/kg + ghrelin 30 μg/kg的联合治疗也增加了食物摄入量。两种生长素释放肽剂量之间或两种剂量的 AlloP 与载体之间的食物摄入量没有显着差异。在电生理学研究中，生理相关浓度的 AlloP 延长了 ARC 和 PVN 分离细胞的自发抑制性突触后电流的电流衰减时间。我们得出结论，AlloP 增强了 ghrelin 的摄食作用，这与生殖周期黄体期相关的摄食过多有潜在相关性。