Chronic treatment with dexamethasone alters clock gene expression and melatonin synthesis in rat pineal gland at night

Abstract

Daniela Meneses-Santos,1 Daniella do Carmo Buonfiglio,2 Rodrigo Antonio Peliciari-Garcia,3 Angela Maria Ramos-Lobo,2 Divanízia do Nascimento Souza,1 Angelo Rafael Carpinelli,2 Carla Roberta de Oliveira Carvalho,2 Rogério Antônio Laurato Sertie,2 Sandra Andreotti,2 Fabio Bessa Lima,2 Solange Castro Afeche,4 Emerson Ticona Fioretto,1 José Cipolla-Neto,2 Anderson Carlos Marçal1 1Department of Morphology, Center of Biological Sciences and Health, Federal University of Sergipe, São Cristóvão, Brazil; 2Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; 3Morphophysiology & Pathology Sector, Department of Biological Sciences, Federal University of São Paulo, São Paulo, Brazil; 4Laboratory of Pharmacology, Butanta Institute, São Paulo, Brazil Background: Melatonin is a neuroendocrine hormone that regulates many functions involving energy metabolism and behavior in mammals throughout the light/dark cycle. It is considered an output signal of the central circadian clock, located in the suprachiasmatic nucleus of the hypothalamus. Melatonin synthesis can be influenced by other hormones, such as insulin and glucocorticoids in pathological conditions or during stress. Furthermore, glucocorticoids appear to modulate circadian clock genes in peripheral tissues and are associated with the onset of metabolic diseases. In the pineal gland, the modulation of melatonin synthesis by clock genes has already been demonstrated. However, few studies have shown the effects of glucocorticoids on clock genes expression in the pineal gland. Results: We verified that rats treated with dexamethasone (2 mg/kg body weight, intraperitoneal) for 10 consecutive days, showed hyperglycemia and pronounced hyperinsulinemia during the dark phase. Insulin sensitivity, glucose tolerance, melatonin synthesis, and enzymatic activity of arylalkylamine N-acetyltransferase, the key enzyme of melatonin synthesis, were reduced. Furthermore, we observed an increase in the expression of Bmal1, Per1, Per2, Cry1, and Cry2 in pineal glands of rats treated with dexamethasone. Conclusion: These results show that chronic treatment with dexamethasone can modulate both melatonin synthesis and circadian clock expression during the dark phase. Keywords: clock genes, glucocorticoids, pineal gland, nocturnal insulinemia, glycemia profile, AANAT activity

Keywords

• Clock genes
• Glucocorticoids
• Pineal gland
• Melatonin