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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Peripheral clock system circadian abnormalities in Cushing's disease

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Author(s):
Soares, Vinicius Reis [1] ; Silva Martins, Clarissa [1] ; Martinez, Edson Zangiacomi [2] ; Araujo, Leonardo Domingues [1] ; Roa, Silvia Liliana Ruiz [1] ; Silva, Lucas Ravagnani [1] ; Moreira, Ayrton Custodio [1] ; De Castro, Margaret [1]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Social Med, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: CHRONOBIOLOGY INTERNATIONAL; v. 37, n. 6 MAY 2020.
Web of Science Citations: 0
Abstract

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. (AU)

FAPESP's process: 14/03989-6 - Uncovering pathophysiological and molecular mechanisms involved in tumorigenesis by platforms for next-generation sequencing (NGS)
Grantee:Margaret de Castro
Support Opportunities: Research Projects - Thematic Grants