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HPA Stress Axis diagram

Understanding the HPA Axis


June 5, 2019 | Published by

If you’re a regular reader of our blog you’ve probably seen the term “HPA Axis” appear frequently. What is this thing, and why do we talk about it so much? The HPA Axis is the term given to the network of parts made up by the hypothalamus, pituitary, and adrenal glands. His network is one of the most important elements of the whole-body process known as homeostasis, which maintains biochemical and physiological balance in your body. (1)

The HPA axis contains a complex set of positive and negative feedback influences between the hypothalamus, pituitary gland, and adrenal gland. These positive and negative feedback mechanisms work in a neuroendocrine manner in order to modulate a number of important physiological processes such as immunity, fertility, and the body’s response to stress. (2)

A negative feedback system works like the thermostat in a house or apartment. The thermostat senses the heat in the room and compares it with the desired temperature at which it has been set. When the heat gets too low, the thermostat signals the relay switch to tell the furnace to ignite, sending out hot air into the room and raising the heat. When the heat has risen to the desired level, the thermostat signals the furnace to quit until more heat is needed. This cycle is called a negative feedback system because when enough heat is released, a negative signal is sent to slow or stop the input. (3)

The HPA Axis is also responsible for adjusting cortisol levels according to the needs of the body. Under normal and stressed conditions, it does this job via a hormone called the Adrenal Corticotrophic Hormone (ACTH). ACTH is secreted from the pituitary gland in response to orders from the hypothalamus and travels in the bloodstream to the adrenal cortex. There it activates cells in all three (or four) zones to produce their various hormones. (3)

Each zone generates different hormones as end products, but the process of making hormones in all zones begins with ACTH binding to the walls of the adrenal cells. This initiates a chain reaction of intracellular enzymes that release cholesterol within the cell. The cholesterol is then used inside the adrenal cells to manufacture pregnenolone, the first hormone in the adrenal cascade. No matter which adrenal hormone is being produced, pregnenolone is the first hormone formed in the series. (3)

Cortisol is responsible for many of the life sustaining functions attributed to the adrenal glands. Although cortisol is secreted by the zona fasciculata in the adrenal glands, it is regulated primarily from the brain. The amount of cortisol circulating at any particular moment is regulated by a complex interaction between the hypothalamus, the pituitary gland, and the adrenal glands. (3)

It is important to support healthy cortisol levels in order to ensure the hypothalamus and pituitary glands preserve the appropriate level of sensitivity to the negative feedback of cortisol. (1) Identifying stressors and working towards a more balanced life is important for your HPA axis to be functioning properly. Make sure you’re getting enough sleep every night, limiting alcohol and caffeine use, and taking note of any other stressors that may be impacting your life.

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To read more on the HPA Axis, check out Dr. Wilson’s book Adrenal Fatigue: The 21st Century Stress Syndrome.

  1. Alschuler, L. The HPA Axis. Integrative Therapeutics Blog.
  2. DeMorrow, S. Role of the Hypothalamic–Pituitary–Adrenal Axis in Health and Disease. International Journal of Molecular Sciences.
  3. Wilson, J. Adrenal Fatigue The 21st Century Stress Syndrome.

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