How the Adrenal Axis Works

What is the adrenal axis?

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

Glucocorticoid production is regulated by the hypothalamic-pituitary-adrenal-axis.

  1. Corticotropin-releasing hormone (CRH) is secreted from the hypothalamus. This release is influenced by stress levelstime of day and serum cortisol levels.
  2. CRH travels in the blood and binds to specific receptors in the pituitary gland. This binding causes increased production of adrenocorticotropic hormone (ACTH).
  3. ACTH is released into the bloodstream and travels to the adrenal glands, where it binds to specific receptors on the adrenal cortex.
  4. This binding of ACTH to the receptors stimulates the adrenal cortex to release cortisol into the bloodstream, where it has a wide range of effects (see below).
  5. Increased serum cortisol levels inhibit the production of CRH and ACTH via negative feedback, preventing the overproduction of cortisol.
Hypothalamic-Pituitary-Adrenal Axis Diagram
Hypothalamic-Pituitary-Adrenal axis diagram

How aldosterone is regulated

1. Low blood volume triggers the 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 the production of Angiotensin II via negative feedback.

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