Hypothalamic-pituitary-adrenocortical HPA axis

Figure 18.3. Endocrine-immune inter-relationship in depression. In depression, the hypothalamic-pituitary-adrenal (HPA) axis is up-regulated with a down-regulation of its negative feedback controls. Corticotrophin releasing factor (CRF) is hypersecreted from the hypothalamus and induces the release of adrenocortico-trophic hormone (ACTH) from the pituitary. ACTH interacts with receptors on adrenocortical cells and cortisol is released from the adrenal glands adrenal hypertrophy can also occur. Release of cortisol into the circulation has a number of effects, including elevation of blood glucose. The negative feedback of cortisol to the hypothalamus, pituitary and immune system is impaired. This leads to continual activation of the HPA axis and excess cortisol release. Cortisol receptors become desensitized leading to increased activity of the pro-inflammatory immune mediators and disturbances in neurotransmitter transmission.

Concentrations of hypothalamic and anterior pituitary peptides and adrenal glucocorticoids are measured accurately and at low concentrations in body fluids using immunoassay and instrumental methods. Relying on basal hormone concentrations for confirmmg adrenocortical dysfunction, however, can be problematic because of the episodic and circadian secretion of the hormones that regulate the HPA axis. For example, some individuals have an abnormality of the HPA axis, but still maintain basal cortisol and ACTH secretion within die reference interval of the normal population. Dynamic testing of the HPA axis helps define abnormalities that are not reflected in basal hormone secretion. 

---