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首页> 外文期刊>EMBO Journal >A secretagogin locus of the mammalian hypothalamus controls stress hormone release
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A secretagogin locus of the mammalian hypothalamus controls stress hormone release

机译：哺乳动物下丘脑的secretagogin轨迹控制应激激素释放

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摘要

A hierarchical hormonal cascade along the hypothalamic-pituitary-adrenal axis orchestrates bodily responses to stress. Although corticotropin-releasing hormone (CRH), produced by parvocellular neurons of the hypothalamic paraventricular nucleus (PVN) and released into the portal circulation at the median eminence, is known to prime downstream hormone release, the molecular mechanism regulating phasic CRH release remains poorly understood. Here, we find a cohort of parvocellular cells interspersed with magnocellular PVN neurons expressing secretagogin. Single-cell transcriptome analysis combined with protein interactome profiling identifies secretagogin neurons as a distinct CRH-releasing neuron population reliant on secretagogin's Ca2+ sensor properties and protein interactions with the vesicular traffic and exocytosis release machineries to liberate this key hypothalamic releasing hormone. Pharmacological tools combined with RNA interference demonstrate that secretagogin's loss of function occludes adrenocorticotropic hormone release from the pituitary and lowers peripheral corticosterone levels in response to acute stress. Cumulatively, these data define a novel secretagogin neuronal locus and molecular axis underpinning stress responsiveness.
机译：一个层次激素级联的肾上腺轴协调身体对压力的反应。促肾上腺皮质激素的释放激素(CRH)生产由parvocellular下丘脑神经元室旁核(PVN)和释放门脉循环正中隆起,知道'下游激素释放,分子机制调节相位的CRH释放仍然知之甚少。parvocellular细胞穿插magnocellular PVN神经元表达secretagogin。结合蛋白质interactome剖析作为一种独特的识别secretagogin神经元CRH-releasing神经元人口依赖secretagogin Ca2 +传感器的特性和蛋白质水泡交通和交互胞外分泌释放机械解放下丘脑释放激素的关键。药理工具结合RNA干扰证明secretagogin的损失的函数阻塞促肾上腺皮质激素从垂体释放,降低外围皮质甾酮水平以应对急性压力。secretagogin神经元位点和分子轴支撑压力响应。

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