The significance of glucocorticoid pulsatility.
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.
Lightman
Stafford L
SL
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY. Stafford.Lightman@bristol.ac.uk
Wiles
Crispin C
CC
Atkinson
Helen C
HC
Henley
David E
DE
Russell
Georgina M
GM
Leendertz
Jack A
JA
McKenna
Mervyn A
MA
Spiga
Francesca
F
Wood
Susan A
SA
Conway-Campbell
Becky L
BL
D000204:Activity Cycles / Q000502:physiology*; D000818:Animals; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000378:metabolism; D013997:Time Factors
D005938:Glucocorticoids