How adrenal axis works

The adrenal axis (hypothalamic-pituitary-adrenal axis) refers to a complex set of interactions and feedback loops between the hypothalamus, pituitary and adrenal glands. This system regulates the body’s response to stress, immune function, energy expenditure, mood, emotions and libido. 

What are the adrenal glands?

  • There is an adrenal gland located above each kidney
  • They produce a number of different hormones
  • The adrenal glands are composed of an outer cortex and an inner medulla

Adrenal cortex

The adrenal cortex is responsible for producing cortisol and aldosterone.


  • Cortisol is a steroid hormone (glucocorticoid)
  • It is released in response to stress and low blood-glucose concentration.
  • Some of its functions include:
    • Increasing blood glucose levels by promoting gluconeogenesis
    • Suppressing the immune system
    • Aiding the metabolism of fat, protein and carbohydrates


  • Aldosterone is also a steroid hormone (mineralocorticoid)
  • Its main function is to increase blood volume
  • It causes reabsorption of sodium and water, in addition to excretion of potassium

Adrenal medulla

  • The adrenal medulla produces adrenaline and noradrenaline (both have similar actions).
  • They are released as an acute response to stress and imitate many of the effects of cortisol
  • They essentially prepare the body for “fight or flight” – ↑HR,  ↑BP,  ↑blood flow to muscles
  • Release is under direct control from the hypothalamus
  • Adrenaline and noradrenaline have a much shorter half life than cortisol

How cortisol is regulated

  1. Corticotropic releasing hormone (CRH) is secreted from the hypothalamus
  2. This release is influenced by stress levels, time of day and serum cortisol levels
  3. CRH travels in the blood and binds to specific receptors in the pituitary gland
  4. This binding causes increased production of adrenocorticotropic hormone (ACTH)
  5. ACTH is released into the bloodstream where it travels to the adrenal glands
  6. ACTH binds to specific receptors in the adrenal cortex
  7. This stimulates the adrenal cortex to release cortisol into the blood
  8. Cortisol enables the body to cope with stress in a more effective manner
  9. Increased levels of cortisol also have an immunosuppressive effect
  10. Blood glucose is also increased via breakdown of glycogen, protein and fat
  11. Increased serum cortisol inhibits production of CRH and ACTH via negative feedback


How aldosterone is regulated

1. Low blood volume triggers release of angiotensin II.
2. Angiotensin II stimulates the adrenal cortex to produce aldosterone.

Aldosterone has a number of different actions:

  • Sodium reabsorption
  • Water reabsorption
  • Potassium excretion

3. Aldosterone’s actions result in a net increase in blood volume.
4. Increased blood volume inhibits production of Angiotensin II via negative feedback.



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