Introduction: Food intake varies during the ovarian hormone/estrous cycle in humans and rodents, an effect mediated mainly by estradiol. A potential mediator of the central anorectic effects of estradiol is the neuropeptide relaxin-3 (RLN3) synthetised in the nucleus incertus (NI) and acting via the relaxin-family peptide-3 receptor (RXFP3). Methods: We investigated the relationship of RLN3/RXFP3 signaling and feeding behavior across the female rat estrous cycle. We used in situ hybridization to investigate expression patterns of Rln3 mRNA in NI and Rxfp3 mRNA in the hypothalamic paraventricular nucleus (PVN), lateral hypothalamic area (LHA), medial preoptic area (MPA), and bed nucleus of the stria terminalis (BNST), across the estrous cycle. We identified expression of estrogen receptors in the NI using droplet digital polymerase-chain reaction and assessed the electrophysiological responsiveness of NI neurons to estradiol in brain slices. Results: Rln3 mRNA reached the lowest levels in the NI pars compacta during proestrus. Rxfp3 mRNA levels varied across the estrous cycle in a region-specific manner, with changes observed in the perifornical LHA, magnocellular PVN, dorsal BNST, and MPA, but not in the parvocellular PVN or lateral LHA. G protein-coupled estrogen receptor-1 (Gper1) mRNA was the most abundant estrogen receptor transcript in the NI. Estradiol inhibited 33% of type I NI neurons, including RLN3-positive cells. Conclusion: These findings demonstrate that the RLN3/RXFP3 system is modulated by the estrous cycle and although further studies are required to better elucidate the cellular and molecular mechanisms of estradiol signaling, current results implicate the involvement of RLN3/RXFP3 system in food intake fluctuations observed across the estrous cycle in female rats.


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喂养和松弛素 3/Rxfp3 mRNA 表达的动情周期调节 - 对雌二醇的影响

简介：在人类和啮齿动物的卵巢激素/发情周期中，食物摄入会发生变化，这种影响主要由雌二醇介导。雌二醇中枢厌食作用的潜在介质是在不定核 (NI) 中合成的神经肽松弛素 3 (RLN3)，并通过松弛素家族肽 3 受体 (RXFP3) 起作用。方法：我们研究了雌性大鼠发情周期中 RLN3/RXFP3 信号与摄食行为的关系。我们使用原位杂交来研究 NI 中 Rln3 mRNA 和下丘脑室旁核 (PVN)、下丘脑外侧区 (LHA)、视前内侧区 (MPA) 和终纹床核 (BNST) 中 Rxfp3 mRNA 的表达模式，跨越发情周期。我们使用液滴数字聚合酶链反应鉴定了 NI 中雌激素受体的表达，并评估了 NI 神经元对脑切片中雌二醇的电生理反应。结果：Rln3 mRNA在发情前期在NI致密部中达到最低水平。Rxfp3 mRNA 水平在整个发情周期中以特定区域的方式变化，在周围 LHA、大细胞 PVN、背侧 BNST 和 MPA 中观察到变化，但在小细胞 PVN 或外侧 LHA 中没有观察到变化。G 蛋白偶联雌激素受体 1 (Gper1) mRNA 是 NI 中最丰富的雌激素受体转录物。雌二醇抑制 33% 的 I 型 NI 神经元，包括 RLN3 阳性细胞。结论：