Di Shi, Tasker Jeffrey G
Neurobiology Division, Department of Cell and Molecular Biology, Tulane University, New Orleans, LA, USA.
Prog Brain Res. 2008;170:379-88. doi: 10.1016/S0079-6123(08)00431-7.
Glucocorticoids secreted in response to stress activation of the hypothalamic-pituitary-adrenal axis feed back onto the hypothalamus to rapidly suppress neuroendocrine activation, including oxytocin and vasopressin secretion. Here we provide a brief review focused on our recent findings of a rapid glucocorticoid-induced opposing regulation of glutamate and gamma-aminobutyric acid (GABA) inputs to magnocellular neurons via the release of distinct retrograde messengers. The stress hormone corticosterone and its synthetic analogue dexamethasone elicit the rapid retrograde release of endocannabinoids by activating a novel membrane-associated, G protein-coupled receptor in parvocellular and magnocellular neuroendocrine cells of the hypothalamic paraventricular and supraoptic nuclei. Glucocorticoids also cause the rapid retrograde release of an unknown messenger that facilitates presynaptic GABA release onto magnocellular neuroendocrine cells. These finding suggest that there is a strict synapse-specific segregation of the opposing actions of the two retrogradely released messengers. Thus, the combined actions of glucocorticoids cause a rapid synaptic inhibition of the magnocellular neurons and would be expected, therefore, to mediate a rapid feedback inhibition of the secretion of oxytocin and vasopressin during stress activation of the hypothalamic-pituitary-adrenal axis.
下丘脑 - 垂体 - 肾上腺轴应激激活时分泌的糖皮质激素会反馈至下丘脑，以迅速抑制神经内分泌激活，包括催产素和血管加压素的分泌。在此，我们简要综述一下近期的研究发现，即糖皮质激素通过释放不同的逆行信使，对大细胞神经元的谷氨酸和γ-氨基丁酸（GABA）输入产生快速的反向调节作用。应激激素皮质酮及其合成类似物地塞米松通过激活下丘脑室旁核和视上核小细胞及大细胞神经内分泌细胞中一种新的膜相关G蛋白偶联受体，引发内源性大麻素的快速逆行释放。糖皮质激素还会导致一种未知信使的快速逆行释放，该信使促进突触前GABA释放至大细胞神经内分泌细胞上。这些发现表明，两种逆行释放信使的反向作用存在严格的突触特异性分离。因此，糖皮质激素的联合作用会导致大细胞神经元的快速突触抑制，进而有望在下丘脑 - 垂体 - 肾上腺轴应激激活期间介导对催产素和血管加压素分泌的快速反馈抑制。
