当前位置: X-MOL 学术Mol. Syst. Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A new model for the HPA axis explains dysregulation of stress hormones on the timescale of weeks.
Molecular Systems Biology ( IF 9.9 ) Pub Date : 2020-07-16 , DOI: 10.15252/msb.20209510
Omer Karin 1 , Moriya Raz 1 , Avichai Tendler 1 , Alon Bar 1 , Yael Korem Kohanim 1 , Tomer Milo 1 , Uri Alon 1
Affiliation  

Stress activates a complex network of hormones known as the hypothalamic–pituitary–adrenal (HPA) axis. The HPA axis is dysregulated in chronic stress and psychiatric disorders, but the origin of this dysregulation is unclear and cannot be explained by current HPA models. To address this, we developed a mathematical model for the HPA axis that incorporates changes in the total functional mass of the HPA hormone‐secreting glands. The mass changes are caused by HPA hormones which act as growth factors for the glands in the axis. We find that the HPA axis shows the property of dynamical compensation, where gland masses adjust over weeks to buffer variation in physiological parameters. These mass changes explain the experimental findings on dysregulation of cortisol and ACTH dynamics in alcoholism, anorexia, and postpartum. Dysregulation occurs for a wide range of parameters and is exacerbated by impaired glucocorticoid receptor (GR) feedback, providing an explanation for the implication of GR in mood disorders. These findings suggest that gland‐mass dynamics may play an important role in the pathophysiology of stress‐related disorders.

中文翻译:

HPA轴的新模型可以在数周的时间内解释压力激素的失调。

压力会激活一个复杂的激素网络,称为下丘脑-垂体-肾上腺(HPA)轴。在慢性压力和精神疾病中,HPA轴失调,但是这种失调的起因尚不清楚,目前的HPA模型无法解释。为了解决这个问题,我们为HPA轴开发了一个数学模型,该模型结合了HPA分泌激素的总功能量的变化。质量变化是由HPA激素引起的,HPA激素是轴中腺体的生长因子。我们发现,HPA轴显示了动态补偿的特性,其中腺体在数周内进行调整以缓冲生理参数的变化。这些质量变化解释了酒精中毒,厌食和产后皮质醇和ACTH动态失调的实验发现。调节异常会在很宽的参数范围内发生,糖皮质激素受体(GR)反馈受损会加剧调节异常,从而为GR在情绪障碍中的意义提供了解释。这些发现表明,腺体动力学可能在应激相关疾病的病理生理中起重要作用。
更新日期:2020-08-01
down
wechat
bug