Ghrelin通过弓状核区域α型雌二醇受体神经元介导雌性小鼠采食调控

Ghrelin Mediate Female Mice Food Intake via Affecting on Estrogen Receptor-alpha Neuron in Arcuate Nucleus

Ghrelin作为一种具有特殊功能的能量调控因子,在能量代谢平衡以及生殖调控研究中被广泛关注,然而其在小鼠性周期变化过程中发挥调控的机制尚不明确。本研究通过腹腔注射ghrelin研究其对小鼠性周期不同阶段采食量及血清中雌二醇浓度的影响,并运用免疫荧光技术鉴定了ghrelin与弓状核(arcuate nucleus,ARC)区域分布的α型雌二醇受体(estrogen receptorα,ERα)神经元之间的共表达情况。结果表明,ghrelin(50μg·kg-1)注射后的2h内可显著促进小鼠发情前期采食量(P<0.05);ghrelin可极显著抑制雌激素的分泌(P<0.01),其他阶段未见显著性差异。同时,ghrelin显著增强小鼠各个性周期中ARC区域的神经元活动(P<0.05或P<0.01),均能直接作用于ARC区域ERα神经元,且在发情前期共表达率最高。因此,我们推论小鼠发情前期,腹腔注射ghrelin可直接作用于下丘脑区域的ERα神经元调控血清中雌二醇浓度,并最终介导雌性小鼠采食。

As the specific energy regulator, the function of ghrelin was widely studied in the energy metabolism and reproduction regulation, but its exact regulatory mechanism in the estrous cycle of mice has still not been elucidated. In this study, by intraperitoneal injection of ghrelin to mice, we investigated its effect on feed intake and serum estradiol concentrations （competitive immunoassay electrochemistry luminescence detection） of mice during different stages of estrous cycle, the co-localization between estrogen receptor α （ERα） and ghrelin which existed in arcuate nucleus （ARC） were also studied by immunofluorescence. In the results, ghrelin （50 μg·kg-1） enhanced the feed intake of mice in protesters, in two hours post injection （P〈0.05）; ghrelin suppressed the concentration of estrogen in serum （P〈0.01）, and there was no significant change in other estrous cycle. Moreover, ghrelin enhanced mice neuron activation （P〈0.05 or P〈0.01）, and ghrelin directly act on ERα neuron in ARC nucleus in whole estrous cycle, and highest co-expression rate was occurred in the proestrus. Thus, we hypothesis that ghrelin has the ability to direct acting on ERα neurons in mice hypothalamus to effect on the concentration of estrogen in serum, and finally mediate mice food behavior in mice protesters.