What is the HPA axis?

One hormone that is of particular interest in depression is the stress hormone cortisol (rodents use the hormone corticosterone rather than cortisol, so human studies measure cortisol while many animal ones measure corticosterone). Cortisol is released at the end of a cascade of hormones. To start with, the hypothalamus (an area on the underside of the brain) releases a hormone called “CRH”. This travels a short way in the blood to the pituitary – a bit of the brain that sort of dangles down below the hypothalamus. CRH causes the pituitary to release a hormone called “ACTH”. This travels around the body in the blood. It activates the adrenal glands. We have two of these, one sitting on the top of each of our kidneys. When ACTH activates the adrenal glands, they release cortisol. Cortisol itself then can travel around the body having lots of effects. For example, is helps prepare muscles in our arms and legs get ready to run away or flight a threat. Cortisol also has effects on the brain. Some cortisol can lead to our thinking being faster and more accurate and our memories being better. Too much cortisol can have the opposite effects.

When we are stressed or feel threatened in some way, the hypothalamus produces more CRH, which leads the pituitary to produce more ACTH, which leads the adrenals to produce more cortisol. The names of the three areas producing the hormones give their initials to the name of the whole system: the “HPA axis”.

HPA axis 1

Negative feedback in the HPA axis

Negative feedback is a means of keeping the body and brain in balance. This happens with the HPA axis as well. When cortisol is released, it causes a reduction in activity in the hypothalamus, reducing the release of CRH, and anterior pituitary, reducing the release of ACTH, reducing the amount of cortisol being released from the adrenal glands. In other words, cortisol is acting to reduce its own the release: the more cortisol there is in the body, the more the HPA axis is inhibited, helping to reduce cortisol levels.

HPA axis glands shutterstock 112081406

Image from Shutterstock- 112081406

Steroids produced in the gonads interact with the HPA axis which leads to sex differences in the function of the HPA axis. The thyroid is a gland in the neck which produces the hormone thyroxine. Thyroid hormones are needed for the body to function effectively.

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