The Origin of Glucocorticoid Hormone Oscillations

• DOI: 10.1371/journal.pbio.1001341
• Publication Date: 2012-06-05T21:12:03Z
• Authors: Jamie J. Walker; Francesca Spiga; Eleanor Waite; Zidong Zhao; Yvonne Kershaw; John R. Terry; Stafford L. Lightman
• Keywords: Male; 0301 basic medicine; 570; 0303 health sciences; QH301-705.5; Corticotropin-Releasing Hormone; 610; Pituitary-Adrenal System; Rats; 3. Good health; Rats, Sprague-Dawley; 03 medical and health sciences; Stress, Physiological; Pituitary Gland; Adrenal Glands; Animals; Biology (General); Corticosterone; Glucocorticoids; Research Article; Signal Transduction

Oscillating levels of adrenal glucocorticoid hormones are essential for optimal gene expression, and for maintaining physiological and behavioural responsiveness to stress. The biological basis for these oscillations is not known, but a neuronal "pulse generator" within the hypothalamus has remained a popular hypothesis. We demonstrate that pulsatile hypothalamic activity is not required for generating ultradian glucocorticoid oscillations. We show that a constant level of corticotrophin-releasing hormone (CRH) can activate a dynamic pituitary-adrenal peripheral network to produce ultradian adrenocorticotrophic hormone and glucocorticoid oscillations with a physiological frequency. This oscillatory response to CRH is dose dependent and becomes disrupted for higher levels of CRH. These data suggest that glucocorticoid oscillations result from a sub-hypothalamic pituitary-adrenal system, which functions as a deterministic peripheral hormone oscillator with a characteristic ultradian frequency. This constitutes a novel mechanism by which the level, rather than the pattern, of CRH determines the dynamics of glucocorticoid hormone secretion.