A new model for the HPA axis explains dysregulation of stress hormones on the timescale of weeks
A new model for the HPA axis explains dysregulation of stress hormones on the timescale of weeks
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DOI：
10.15252/msb.20209510
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发表时间：
2020-07-01
影响因子：
9.9
通讯作者：
Alon, Uri
中科院分区：
文献类型：
--
作者：
Karin, Omer;Raz, Moriya;Alon, Uri
压力会激活一个复杂的荷尔蒙网络，称为下丘脑-垂体-肾上腺(HPA)轴。HPA轴在慢性应激和精神障碍中是失调的，但这种失调的起源尚不清楚，也无法用当前的HPA模型来解释。为了解决这一问题，我们开发了一个HPA轴的数学模型，该模型包含了HPA激素分泌腺的总功能质量的变化。这些质量变化是由HPA荷尔蒙引起的，HPA荷尔蒙充当轴上腺体的生长因子。我们发现，HPA轴表现出动态补偿的特性，腺体质量在几周内进行调整，以缓冲生理参数的变化。这些质量变化解释了酒精中毒、厌食症和产后皮质醇和ACTH动力学失调的实验结果。糖皮质激素受体(GR)反馈受损会加剧调节失调，这为GR在情绪障碍中的意义提供了解释。这些发现表明，腺体-质量动力学可能在应激相关疾病的病理生理学中发挥重要作用。
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.