Figure 1.

Ultradian rhythms of the hypothalamic–pituitary–adrenal (HPA) axis and glucocorticoid rhythms. The hypothalamic paraventricular nucleus (PVN) receives circadian input from the suprachiasmatic nucleus of the hypothalamus and stress inputs from the brainstem and from regions of the limbic system such as the hippocampus and amygdala. The PVN projects to the median eminence where it releases corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) into the hypothalamic-pituitary portal circulation. CRH passes through this vascular route to access corticotroph cells in the anterior pituitary, which respond with the rapid release of adrenocorticotropic hormone (ACTH) from preformed vesicles into the general circulation. In turn, ACTH reaches the adrenal cortex where it activates the synthesis and secretion of glucocorticoid hormones (CORT). CORT regulate the activity of the HPA axis, and thus their own production, through feedback mechanisms acting at the level of the pituitary gland where they inhibit ACTH release, and at the level of the PVN where they inhibit the release of CRH and AVP. Under basal (i.e., unstressed) conditions, an ultradian pattern of secretion underlies all the components of the HPA axis. Note that in the rat, CRH pulse frequency is higher (∼3 pulses/h) than the near-hourly oscillation in ACTH and CORT. Reproduced with permission from (Spiga et al., 2014).