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Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
Daily corticosterone rhythm modulates pineal function through NFκB-related gene transcriptional program
Sanseray da Silveira Cruz-Machado1, Eduardo K Tamura1,2, Claudia E Carvalho-Sousa1
1Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil.
Glucocorticoids, like corticosterone, influence daily rhythms and defense gene expression. This study shows corticosterone regulates nocturnal melatonin synthesis by affecting NFκB in the pineal gland.
Area of Science:
- Endocrinology
- Chronobiology
- Molecular Biology
Background:
- Melatonin and glucocorticoids are crucial hormones regulating daily rhythms and immune responses.
- Corticosterone and melatonin exhibit distinct nocturnal patterns, with potential interactions between adrenal and pineal glands.
- Inflammatory conditions suggest a link where corticosterone may enhance melatonin synthesis via NFκB inhibition.
Purpose of the Study:
- To elucidate the crosstalk between adrenal and pineal glands under physiological conditions.
- To investigate the influence of corticosterone rhythm on pineal gland gene expression and melatonin synthesis.
- To understand the role of NFκB in mediating glucocorticoid effects on nocturnal melatonin production.
Main Methods:
- Gene expression analysis of defense response genes in the rat pineal gland at darkness onset.
- Pharmacological inhibition of glucocorticoid receptors using mifepristone.
- Assessment of Aanat gene expression and nocturnal melatonin synthesis.
Main Results:
- A significant reduction in 70 out of 84 defense response genes was observed at darkness onset.
- Mifepristone administration altered the expression of 13 genes and impaired nocturnal melatonin synthesis.
- Corticosterone rhythm was shown to modulate pineal gland phenotype, including Aanat expression.
Conclusions:
- The daily rhythm of corticosterone influences the pineal gland's response to darkness.
- Glucocorticoids regulate nocturnal melatonin synthesis through the NFκB transcriptional pathway.
- This highlights a coordinated regulation of the pineal gland by both the central clock and adrenal hormones.
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