Circadian CLOCK-Mediated Regulation of Target-Tissue Sensitivity to Glucocorticoids: Implications for Cardiometabolic Diseases

Dec 18, 2010Endocrine development

Body clock control of tissue response to stress hormones and its links to heart and metabolism diseases

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Abstract

Glucocorticoids fluctuate in a circadian manner and may influence the transcriptional activity of the glucocorticoid receptor (GR).

  • The Clock protein represses GR activity by modifying specific lysine residues in the receptor.
  • This repression of GR activity oscillates in opposition to the HPA axis's diurnal fluctuations.
  • Mild increases in cortisol, associated with chronic stress, can lead to functional hypercortisolism.
  • Disruptions in the synchronization between the SCN CLOCK and the HPA axis could contribute to metabolic syndrome and cardiovascular issues.

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