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Analysis of the peripheral clock system on Cushing's Syndrome

Grant number: 11/21942-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2012
Effective date (End): April 30, 2013
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Margaret de Castro
Grantee:Lucas Ravagnani Silva
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Glucocorticoids regulate a large number of functions, including metabolic control, the cardiovascular, immune and nervous systems, and influence and modulate the behavior. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) and the resulting chronic exposure to high levels of glucocorticoids cause lots of systemic manifestations, such as obesity with increased visceral fat accumulation, skin changes, cardiovascular abnormalities like hypertension, neuropsychiatric abnormalities, reproductive, endocrine and metabolic disorders like insulin resistance and dyslipidemia, as observed in Cushing's Syndrome. The HPA axis is regulated by the circadian clock system (System Clock), thus circulating levels of glucocorticoids are regulated and naturally fluctuate over 24 hours. Conversely, the HPA axis influences the circadian CLOCK system. In this study, gene expression of the peripheral CLOCK system (Clock gene, BMAL1, per1, Per2, Per3, Cry1Ô and cry2) will be evaluated by real-time PCR (TaqMan). We will study 15 subjects with Cushing's syndrome to compare with 15 healthy subjects. The biochemical analysis will be conducted of blood glucose and lipid profile and salivary cortisol concentrations at baseline, and after inhibition test of the HPA axis by 1 mg of dexamethasone. The analysis of gene expression of the peripheral CLOCKs will be made using peripheral blood sample. Differences between the groups will be analyzed by nonparametric methods using the Mann-Whitney and Fisher's exact test. Correlations will be calculated by the Spearman test. The level of significance is p <0.05.