The hypothalamic, pituitary, adrenal (HPA) axis is our central stress response system and combines the stimuli form the central nervous system as well as the endocrine system..

The HPA is responsible for how we respond to stress. This response is characterized by the release of corticotropin-releasing hormone (CRF) from our hypothalamus, a portion of the brain that contains a number of small nuclei with a variety of functions. When this hormone binds to the anterior pituitary gland, another hormone is released. This is known as the adrenocorticotropic hormone (ACTH), which in turn binds to the adrenal cortex and stimulates release of cortisol. The adrenal cortex is the outer portion of the adrenal gland located on top of each kidney. In response to stress, cortisol is released for several hours after encountering the stressor. A stressor is a chemical or biological agent, environmental condition, external stimulus or an event that causes stress (i.e elevated sound levels, over-illumination, overcrowding, traffic, demanding work load). Cortisol is released to reduce the stressor and ‘calm’ the organism (body and mind). It does that by sending a message or negative feedback to both the hypothalamus with the instruction to stop the release of CRF and to the pituitary with the instruction to stop releasing ACTH.

However, with repeated exposure to stress, the body and mind get used to be exposed to stressors and consequently, the HPA is continually activated, with the inevitable fatigue experienced by the adrenal cortex and decline of cortisol overtime. Therefore, it is important to support healthy cortisol levels and adrenal function in order to ensure the hypothalamus and pituitary glands keep on responding adequately to the release of cortisol. Interestingly, with aging and chronic ongoing stress, the hypothalamus and pituitary are less sensitive to negative feedback from cortisol, whilst both ACTH and cortisol levels rise as we age. Older women secrete more cortisol in response to stress than do older men. Young women, however, produce lower levels of cortisol in response to stress than do young men.  Thus, it is not just enough to address various health consequences of stress. It is essential to restore homeostasis to the HPA axis.