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The HPA Axis

The hypothalamic, pituitary, adrenal (HPA) axis is our central stress response system. The HPA axis is an eloquent and every-dynamic intertwining of the central nervous system and endocrine system.

This system works in a fairly straight-forward manner. The HPA is responsible for the adaptation component of the stress response. This response is characterized by hypothalamic release of corticotrophin-releasing hormone (CRF). When CRF binds to CRF receptors on the anterior pituitary gland, adrenocorticotropic hormone (ACTH) is released. ACTH binds to receptors on the adrenal cortex and stimulates adrenal release of cortisol. In response to stress, cortisol will be released for several hours after encountering the stressor. At a certain blood concentration of cortisol this protection is ostensibly achieved and the cortisol exerts negative feedback to the hypothalamic release of CRF and the pituitary release of ACTH (negative feedback). At this point, systemic homeostasis returns. (See picture below.)

HPA axis diagram

With repeated exposure to stress (ors), the organism habituates to the stressor with repeated and sustained HPA axis activation. Therefore, it is important to support healthy cortisol levels in order to ensure the hypothalamus and pituitary glands maintain the appropriate level of sensitivity to the negative feedback of cortisol. Central secretion of phase 1 alarm chemicals such as epinephrine and norepinephrine as well as HPA axis activation and secretion of CRF, ACTH and cortisol persist. Interestingly, with aging, the hypothalamus and pituitary are less sensitive to negative feedback from cortisol and both ACTH and cortisol levels rise as we age (1). 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. Women at all ages produce more IL-6 and TNFα as a part of the initial, resistance, phase of the stress response. (2)

Under conditions of normal exposure to cortisol, our tissues only experience fleeting glimpses of the alarm catecholamine’s and cortisol. Thus, as we are addressing the various health consequences of stress, it is imperative to also address the axis of response itself and attempt to restore homeostasis to the HPA axis.

Credit: Lise Alschuler, ND

  1. Veldhuis JD, et al. Endocrinol Metab Clin North Am. 2013 Jun;42(2):201-25.
  2. Seeman TE, et al. Psychoneuroendocrinology. 2001;26(3):225