Analysis of the Peripheral CLOCK System on Cushing's Syndrome

• Grant number: 11/21942-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2012
• End date: April 30, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Margaret de Castro
• Grantee: Lucas Ravagnani Silva
• Host 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 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 them 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 a 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.(AU)