Ghrelin activates hypophysiotropic corticotropin-releasing factor neurons independently of the arcuate nucleus.
Ghrelin activates hypophysiotropic corticotropin-releasing factor neurons independently of the arcuate nucleus.
复制标题
生长素独立于弓状核激活促垂体促肾上腺皮质激素释放因子神经元。
DOI：
10.1016/j.psyneuen.2016.01.027
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发表时间：
2016-05
影响因子：
3.7
通讯作者：
Perello M
中科院分区：
文献类型：
--
作者：
Cabral A;Portiansky E;Sánchez-Jaramillo E;Zigman JM;Perello M
以前的工作已经确定，激素ghrelin通过激活下丘脑室旁核（PVN）的促肾上腺皮质激素释放因子（CRF）神经元参与下丘脑-垂体-肾上腺神经内分泌轴。目前尚不清楚介导生长激素释放肽这种作用的神经元回路。在这里，我们表明，生长素释放肽诱导的PVN CRF神经元的激活涉及抑制γ-氨基丁酸（GABA）的输入，可能是通过生长素释放肽结合位点，定位在GABA能终端的PVN内。虽然在存在神经肽Y（NPY）受体拮抗剂的情况下或在弓状核（ARC）消融的小鼠中，ghrelin激活PVN CRF神经元，但在ghrelin受体表达限于ARC agglutinase基因相关蛋白（AgRP）/NPY神经元的小鼠中，它未能做到这一点。这些数据支持这样的观点，即ghrelin通过抑制局部GABA能紧张，以ARC非依赖性方式激活PVN CRF神经元。此外，这些数据表明，神经回路介导生长激素释放肽的食欲活动与其作为压力信号的作用是解剖学分离的。
Previous work has established that the hormone ghrelin engages the hypothalamic-pituitary-adrenal neuroendocrine axis via activation of corticotropin-releasing factor (CRF) neurons of the hypothalamic paraventricular nucleus (PVN). The neuronal circuitry that mediates this effect of ghrelin is currently unknown. Here, we show that ghrelin-induced activation of PVN CRF neurons involved inhibition of γ-aminobutyric acid (GABA) inputs, likely via ghrelin binding sites that were localized at GABAergic terminals within the PVN. While ghrelin activated PVN CRF neurons in the presence of neuropeptide Y (NPY) receptor antagonists or in arcuate nucleus (ARC)-ablated mice, it failed to do it so in mice with ghrelin receptor expression limited to ARC agouti gene related protein (AgRP)/NPY neurons. These data support the notion that ghrelin activates PVN CRF neurons via inhibition of local GABAergic tone, in an ARC-independent manner. Furthermore, these data suggest that the neuronal circuits mediating ghrelin’s orexigenic action vs. its role as a stress signal are anatomically dissociated.