Rapid intra-adrenal feedback regulation of glucocorticoid synthesis.
Rapid intra-adrenal feedback regulation of glucocorticoid synthesis.
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DOI：
10.1098/rsif.2014.0875
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发表时间：
2015-01-06
期刊：
影响因子：
--
通讯作者：
Terry JR
中科院分区：
文献类型：
--
作者：
Walker JJ;Spiga F;Gupta R;Zhao Z;Lightman SL;Terry JR
下丘脑-垂体-肾上腺轴是调节肾上腺糖皮质激素分泌的重要神经内分泌系统。该系统的特点是动态的超昼夜激素振荡，此外是高度响应压力刺激。我们最近发现，产生这种超日节律的主要机制是系统水平的相互作用，其中垂体释放的促肾上腺皮质激素（ACTH）刺激肾上腺糖皮质激素的分泌，这反过来又在垂体水平反馈，迅速抑制ACTH分泌。在这项研究中，我们联合收割机实验生理学和数学建模来研究肾上腺内调节糖皮质激素合成的机制。我们的建模结果表明，糖皮质激素可以通过非常快速（几分钟内），推测非基因组，肾上腺内途径抑制自己的合成。我们提出了进一步的证据，在这种肾上腺内抑制存在一个短的时间延迟，也在每个ACTH刺激的启动，这种局部反馈机制被迅速拮抗，大概是通过激活特定的ACTH受体（MC 2 R）信号通路。这种肾上腺内抑制机制使肾上腺能够快速释放糖皮质激素，同时防止糖皮质激素响应于与应激相关的ACTH的大幅激增而不受控制地释放。
The hypothalamic–pituitary–adrenal axis is a vital neuroendocrine system that regulates the secretion of glucocorticoid hormones from the adrenal glands. This system is characterized by a dynamic ultradian hormonal oscillation, and in addition is highly responsive to stressful stimuli. We have recently shown that a primary mechanism generating this ultradian rhythm is a systems-level interaction where adrenocorticotrophin hormone (ACTH) released from the pituitary stimulates the secretion of adrenal glucocorticoids, which in turn feedback at the level of the pituitary to rapidly inhibit ACTH secretion. In this study, we combine experimental physiology and mathematical modelling to investigate intra-adrenal mechanisms regulating glucocorticoid synthesis. Our modelling results suggest that glucocorticoids can inhibit their own synthesis through a very rapid (within minutes), presumably non-genomic, intra-adrenal pathway. We present further evidence for the existence of a short time delay in this intra-adrenal inhibition, and also that at the initiation of each ACTH stimulus, this local feedback mechanism is rapidly antagonized, presumably via activation of the specific ACTH receptor (MC2R) signalling pathway. This mechanism of intra-adrenal inhibition enables the gland to rapidly release glucocorticoids while at the same time preventing uncontrolled release of glucocorticoids in response to large surges in ACTH associated with stress.
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DOI：
10.1152/ajpendo.1997.273.2.e363
发表时间：
1997-08-01
影响因子：
5.1
作者：
Jasper, MS;Engeland, WC
通讯作者：
Engeland, WC
影响因子：
4.8
作者：
PERON, FG;MONCLOA, F;DORFMAN, RI
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DORFMAN, RI
DOI：
10.1111/j.1749-6632.1987.tb24976.x
发表时间：
1987-12-31
影响因子：
5.2
作者：
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通讯作者：
SHINSAKO, J
影响因子：
2.8
作者：
Chacón, F;Esquifino, AI;Alvarez, MP
通讯作者：
Alvarez, MP
DOI：
10.1073/pnas.220413297
发表时间：
2000-10-24
影响因子：
11.1
作者：
Doucas, V;Shi, YH;Evans, RM
通讯作者：
Evans, RM