The HPA-axis and Stress Response


The hypothalamic-pituitary-adrenal (HPA) axis is the body’s primary response system to stress. As key parts of the endocrine system, the components of HPA-axis work together to prepare the body to respond to stressors, mental or physical, by either priming or suppressing metabolic processes throughout the body.

The primary interface between the central nervous system and the endocrine system is the hypothalamus. Found in all vertebrates, the human hypothalamus is about the size of a pea and generates hormonal secretions that stimulate a response in endocrine organs throughout the body.

Specific to the HPA-axis, a stressor stimulates the hypothalamus to release corticotrophin releasing factor (CRF). In the HPA-axis cascade, CRF travels to the anterior pituitary gland via the hypophyseal portal system, where it triggers the release of adrenocorticotrophic hormone (ACTH) into the bloodstream. ACTH travels through the body’s vascular network, where the cortex of the adrenal gland detects its presence and stimulates the release of cortisol. Cortisol, in turn, affects energy distribution throughout the body, diverting resources from other activities—e.g., immune response, digestion, or reproduction—in order to mobilize energy for a potential “fight-or-flight” confrontation.

As cortisol levels build, another important function of the hormone takes effect. High levels of cortisol trigger a negative feedback loop to the pituitary gland and the hypothalamus that suppresses the stress response, allowing the system to normalize.

If cortisol levels remain elevated for a prolonged time, however, such as through repeated stressor exposure or a failure of the feedback loop, research has revealed a long list of potential negative outcomes. Primary amongst these are hypertension, depression, and a suppressed immune response. Other possible effects include loss of appetite—which may be accompanied by weight loss or muscle wasting—ulcers, and reproductive impairment.

The HPA-axis cascade causes effects that manifest in nearly every part of the body. Stay up-to-date on current findings and discussion with the following selection of research articles and commentary focusing on the HPA-axis and stress response.