Circadian rhythms of glucocorticoid hormone actions in target tissues: Potential clinical implications

Research output: Contribution to journalReview article

20 Citations (Scopus)

Abstract

Organisms face unforeseen short- and long-term changes in the environment (stressors). To defend against these changes, organisms have developed a stress system that includes the hypothalamic-pituitary-adrenal (HPA) axis, which employs glucocorticoids and the glucocorticoid receptor (GR) for signal transduction. In addition, organisms live under the strong influence of day-night cycles and, hence, have also developed a highly conserved circadian clock system for adjusting their activities to recurring environmental changes. This regulatory system creates and maintains internal circadian rhythmicity by employing a self-oscillating molecular pacemaker composed of the Clock-Bmal1 heterodimer and other transcription factors. The circadian clock consists of a central master clock in the suprachiasmatic nucleus of the brain hypothalamus and peripheral slave clocks in virtually all organs and tissues. The HPA axis and the circadian clock system communicate with each other at multiple levels. The central clock controls the HPA axis, creating the diurnal oscillation of circulating adrenocorticotropic hormone and cortisol, and the HPA axis adjusts the circadian rhythmicity of the peripheral clocks in response to various stressors through the GR. Further, Clock-Bmal1 regulates the response to glucocorticoids in peripheral tissues through acetylation of the GR, possibly antagonizing the biologic actions of diurnally fluctuating circulating cortisol. Importantly, dysregulation in the clock system and the HPA axis may cause similar pathologic manifestations - including obesity, metabolic syndrome, and cardiovascular disease - by uncoupling circulating cortisol concentrations from tissue sensitivity to glucocorticoids.

Original languageEnglish
Article numberpt4
JournalScience Signaling
Volume5
Issue number244
DOIs
Publication statusPublished - 2 Oct 2012
Externally publishedYes

Fingerprint

Circadian Clocks
Glucocorticoid Receptors
Circadian Rhythm
Glucocorticoids
Hydrocortisone
Clocks
Hormones
Periodicity
Tissue
Pituitary-Adrenal System
Slaves
Suprachiasmatic Nucleus
Metabolic Diseases
Acetylation
Adrenocorticotropic Hormone
Hypothalamus
Signal Transduction
Transcription Factors
Cardiovascular Diseases
Obesity

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Circadian rhythms of glucocorticoid hormone actions in target tissues : Potential clinical implications. / Kino, Tomoshige.

In: Science Signaling, Vol. 5, No. 244, pt4, 02.10.2012.

Research output: Contribution to journalReview article

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