Circadian endocrine rhythms: The hypothalamic-pituitary-adrenal axis and its actions

Nicolas C. Nicolaides, Evangelia Charmandari, George P. Chrousos, Tomoshige Kino

Research output: Contribution to journalArticle

72 Citations (Scopus)


The stress system effectively restores the internal balance-or homeostasis-of living organisms in the face of random external or internal changes, the stressors. This highly complex system helps organisms to provide a series of neuroendocrine responses to stressors-the stress response-through coordinated activation of the hypothalamic-pituitary-adrenal (HPA) axis and the locus coeruleus/norepinephrine autonomic nervous systems. In addition to stressors, life is influenced by daily light/dark changes due to the 24-h rotation of Earth. To adjust to these recurrent day/night cycles, the biological clock system employs the heterodimer of transcription factors circadian locomotor output cycle kaput/brain-muscle-arnt-like protein 1 (CLOCK/BMAL1), along with a set of other transcription factors, to regulate the circadian pattern of gene expression. Interestingly, the stress system, through the HPA axis, communicates with the clock system; therefore, any uncoupling or dysregulation could potentially cause several disorders, such as metabolic, autoimmune, and mood disorders. In this review, we discuss the biological function of the two systems, their interactions, and the clinical implications of their dysregulation or uncoupling.

Original languageEnglish
Pages (from-to)71-80
Number of pages10
JournalAnnals of the New York Academy of Sciences
Issue number1
Publication statusPublished - May 2014



  • Acetylation
  • Circadian clock system
  • Glucocorticoid receptor
  • Glucocorticoids
  • HPA axis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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