The significance of glucocorticoid pulsatility

• Published in: European journal of pharmacology Vol. 583; no. 2; pp. 255 - 262
• Main Authors: Lightman, Stafford L., Wiles, Crispin C., Atkinson, Helen C., Henley, David E., Russell, Georgina M., Leendertz, Jack A., McKenna, Mervyn A., Spiga, Francesca, Wood, Susan A., Conway-Campbell, Becky L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 07-04-2008
• Subjects: Activity Cycles - physiology; Animals; Glucocorticoid receptor; Glucocorticoids - metabolism; Humans; Hypothalamo-Hypophyseal System - metabolism; Mineralocorticoid receptor; Pituitary-Adrenal System - metabolism; Proteasome; Rats; Signal Transduction - physiology; Stress, Physiological - metabolism; Time Factors; Ultradian rhythm; Mineralocorticoid receptor; Ultradian rhythm; Glucocorticoid receptor; Proteasome
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2007.11.073

Glucocorticoids are secreted in discrete pulses resulting in an ultradian rhythm in all species that have been studied. In the rat there is an approximately hourly rhythm of corticosterone secretion, which appears to be regulated by alternating activation and inhibition of the HPA axis. At the level of signal transduction, the response to these pulses of corticosterone is determined by its dynamic interaction with the two transcription factors — the glucocorticoid and mineralocorticoid receptors. While the mineralocorticoid receptor remains activated throughout the ultradian cycle, the glucocorticoid receptor shows a phasic response to each individual pulse of corticosterone. This phasic response is regulated by an intranuclear proteasome-dependent rapid downregulation of the activated glucocorticoid receptor.