Address for correspondence: Dr E. Kassi, Department of Biological Chemistry, Medical School, Athens University, 75 Mikras Asias Str., Goudi 11527, Athens, Greece. E-mail: ekassi@med.uoa.gr Received 22-11-2012, Accepted 12-02-2013 are secreted in the portal system in a circadian and highly concordant pulsatile fashion. The activity of the HPA axis is in fact characterized not only by a classic circadian rhythm, but also by an ultradian pattern of discrete pulsatile release of glucocorticoids. Glucocorticoids are the final effectors of the HPA axis. These hormones are pleiotropic and exert their effects through their ubiquitously distributed intracellular glucocorticoid receptors alpha and beta (GRα and GRβ, respectively), both members of the nuclear receptor superfamily. The circadian release of ACTH/cortisol in their characteristic pulsatile manner appears to be controlled by one or more pace makers, whose exact location in the brain has not as yet been fully explored in humans. These diurnal variations are perturbed during daily activities like eating, sleeping, etc., while they are more greatly disrupted under stress conditions.