Cortisol is released from the
adrenal glands following activation by
ACTH release from the
pituitary. The ACTH release creating the cortisol awakening response is strongly inhibited after intake of a low-dose
dexamethasone. This is a synthetic
glucocorticoid and this inhibition allows the detection of the presence of
negative feedback from circulating cortisol that controls to
ACTH-secreting cells of the pituitary. In the
hypothalamic-pituitary-adrenal axis the pituitary release of ACTH is regulated by the
hypothalamus. This occurs through the hypothalamus's production of the hypophysiotropic hormone
corticotropin-releasing hormone, the production of which is subject to circadian influence and the day/night cycle. In the cortisol awakening response, the hypothalamic-pituitary-adrenal axis is controlled by the
hippocampus. For example, cortisol awakening response is absent in those with bilateral and unilateral hippocampus damage and hippocampal
atrophy. Those with severe
amnesia, and thus with presumed damage to the
temporal lobe, also do not have it. Those with a larger hippocampus have a greater response. It's plausible also that the
suprachiasmatic nucleus, the light-sensitive biological clock, plays a role in cortisol awakening response regulation. ==Function==