Children's Health Research Institute, London, ON, Canada.
Lawson Health Research Institute, London, ON, Canada.
Front Endocrinol (Lausanne). 2024 Oct 22;15:1459724. doi: 10.3389/fendo.2024.1459724. eCollection 2024.
This review describes the impact of COVID-19 on the endocrine system, focusing on cortisol signaling and growth factor-induced endocrine resistance. As expected, SARS-CoV-2 infection induces systemic inflammation, resulting in stimulation of the adrenal glands leading to elevated cortisol levels with normal adrenocorticotropic hormone (ACTH) levels. The cytokine storm could also stimulate cortisol production. However, in some instances, cortisol levels rise independently of ACTH due to a phenomenon known as "pseudo-Cushing's syndrome," where adrenal glands become less responsive to ACTH. Plasma proteomic analyses showed that this pattern was variably observed among COVID-19 patients, potentially involving calcium dysregulation and GNAS-regulated activities, ultimately impacting the regulation of microvascular permeability. COVID-19 also exhibited a syndrome resembling endocrine resistance, governed by receptor tyrosine kinase signaling pathways. Mild cases displayed elevated activity of EGFR and MMP9, along with increased expression of survival factors like Bax and Bcl2. In contrast, more severe cases involved IGFR-I and enhanced NOTCH signaling, with altered expression of Bcl2, AKT1, and MAPK8. In summary, these findings describe the complex interplay between COVID-19 and endocrine pathology, particularly endocrine resistance. These insights suggest potential endocrine targets for therapeutic interventions to improve short- and long-term outcomes for COVID-19 patients.
这篇综述描述了 COVID-19 对内分泌系统的影响，重点关注皮质醇信号和生长因子诱导的内分泌抵抗。正如预期的那样，SARS-CoV-2 感染会引发全身炎症，导致肾上腺受到刺激，从而导致皮质醇水平升高，而促肾上腺皮质激素（ACTH）水平正常。细胞因子风暴也可能刺激皮质醇的产生。然而，在某些情况下，皮质醇水平的升高与 ACTH 无关，这是一种被称为“假性库欣综合征”的现象，此时肾上腺对 ACTH 的反应性降低。血浆蛋白质组学分析表明，这种模式在 COVID-19 患者中存在差异，可能涉及钙失调和 GNAS 调节的活性，最终影响微血管通透性的调节。COVID-19 还表现出一种类似于内分泌抵抗的综合征，由受体酪氨酸激酶信号通路控制。轻度病例表现出 EGFR 和 MMP9 的活性升高，以及生存因子 Bax 和 Bcl2 的表达增加。相比之下，更严重的病例涉及 IGFR-I 和增强的 NOTCH 信号，Bcl2、AKT1 和 MAPK8 的表达发生改变。总之，这些发现描述了 COVID-19 与内分泌病理学之间的复杂相互作用，特别是内分泌抵抗。这些研究结果表明，针对这些潜在的内分泌靶点进行治疗干预可能会改善 COVID-19 患者的短期和长期预后。
