# Transcript

This shows the HPA axis in a ‘resting’ or ‘baseline’ state. A small amount of the hormone cortisol, a glucocorticoid, is secreted continually from the adrenal cortex into the bloodstream. Cortisol is broken down by enzymes in the blood, so levels in the blood remain low.

When a stressor is perceived the brain triggers a cascade of events that leads to a surge in the level of cortisol secreted by the adrenal cortex. In this next sequence you will see the events involved in this cascade, and how feedback loops operate to return the activity of the HPA axis and levels of cortisol back to baseline.

When we see, hear or think of something that is frightening, the sensory and higher reasoning centres in the cortex are activated. The cortex then sends a message to the amygdala.

The amygdala releases corticotropin releasing factor, or CRF, which activates the hypothalamus. As a result the hypothalamus also releases CRF which activates the pituitary gland, eliciting release of adrenocorticotropic hormone, or ACTH, into the blood.

ACTH stimulates the adrenal cortex to release cortisol into the bloodstream.

Cortisol travels to the prefrontal cortex, the hippocampus, the hypothalamus, and the pituitary which all carry glucocorticoid receptors.

Cortisol stimulates the prefrontal cortex and hippocampus to send signals to inhibit the activity of the hypothalamus. Cortisol also has a direct inhibitory effect on the activity of the hypothalamus and pituitary.

So indirectly or directly, cortisol inhibits the hypothalamus and the pituitary causing secretion of CRF and ACTH to decline.

As stimulation by ACTH of the adrenal cortex declines, the amount of cortisol secreted also falls. So cortisol levels normally have a lowering, or negative, effect on their own levels – this is a negative feedback system. Cortisol is also broken down in the blood. So after a stressor has disappeared cortisol levels return fairly quickly to baseline levels.

If an external stressor remains, or if an individual continues to feel threatened, the stress response is prolonged. What happens if the HPA axis is stimulated chronically?

If stress is chronic the HPA axis is being constantly triggered to secrete cortisol. Levels of cortisol in the blood climb as the breakdown of cortisol by enzymes in the blood cannot keep pace with the amount released. So if stress becomes chronic, the blood levels of cortisol are elevated.

The constant barrage of cortisol has a toxic effect on glucocorticoid receptors, which decline in number and influence.

This results in reduction of inhibition on the hypothalamus and pituitary, so CRF and ACTH continue to be released, and the adrenal cortex continues to be stimulated to release cortisol.

So when the HPA axis is over-stimulated, high levels of cortisol in the blood drive the levels of cortisol in the blood even higher – this ‘runaway’ effect is called positive feedback.