In Cushing’s syndrome, the cortisol rhythm is impaired and can be associated with the disruption in the rhythmic expression of clock genes. In this study, we evaluated the expression of CLOCK, BMAL1, CRY1, CRY2, PER1, PER2, PER3 genes in peripheral blood leukocytes of healthy individuals (n = 13) and Cushing’s disease (CD) patients (n = 12). Participants underwent salivary cortisol measurement at 0900 h and 2300 h. Peripheral blood samples were obtained at 0900 h, 1300 h, 1700 h, and 2300 h for assessing clock gene expression by qPCR. Gene expression circadian variations were evaluated by the Cosinor method. In healthy controls, a circadian variation in the expression of CLOCK, BMAL1, CRY1, PER2, and PER3 was observed, whereas the expression of PER1 and CRY2 followed no specific pattern. The expression of PER2 and PER3 in healthy leukocytes presented a late afternoon acrophase, similarly to CLOCK, whereas CRY1 showed night acrophase, similarly to BMAL1. In CD patients, the circadian variation in the expression of clock genes was lost, along with the abolition of cortisol circadian rhythm. However, CRY2 exhibited a circadian variation with acrophase during the dark phase in patients. In conclusion, our data suggest that Cushing’s disease, which is characterized by hypercortisolism, is associated with abnormalities in the circadian pattern of clock genes. Higher expression of CRY2 at night outlines its putative role in the cortisol circadian rhythm disruption.

在库欣氏综合症中，皮质醇节律受损，并且可能与时钟基因节律表达的破坏有关。在这项研究中，我们评估了健康个体（n = 13）和库欣病（CD）（n = 12）患者外周血白细胞中CLOCK，BMAL1，CRY1，CRY2，PER1，PER2，PER3基因的表达。参与者在0900 h和2300 h进行唾液皮质醇测量。在0900h，1300h，1700h和2300h获得外周血样品，以通过qPCR评估时钟基因表达。通过Cosinor方法评估基因表达的昼夜节律变异。在健康对照中，观察到CLOCK，BMAL1，CRY1，PER2和PER3表达的昼夜节律变化，而PER1和CRY2没有遵循特定的模式。在健康的白细胞中，PER2和PER3的表达与下午CLOCK相似，表现为下午晚期，而CRY1与BMAL1相似，表现为夜间相似。在CD患者中，时钟基因表达的昼夜节律变异消失，同时皮质醇昼夜节律消失。然而，在患者的黑暗期中，CRY2显示出与顶体相有关的昼夜节律变化。总之，我们的数据表明，以皮质醇过多症为特征的库欣氏病与时钟基因的昼夜节律异常有关。更高表达晚上的CRY2概述了其在皮质醇昼夜节律紊乱中的假定作用。