The Role of the HPA Axis in Stress
A skin blanching test involves pressing the skin to see if the redness or discoloration disappears.
Stress and HPA Axis
The Role of the HPA Axis in Stress, Scientifically, stress is defined as a state of real or perceived threat to homeostasis or internal dynamic balance. 1-4 Stress has many effects on the body and is closely related to inflammation, activating inflammatory pathways in the brain and peripheral tissues. 5 Chronic stress can cause permanent physiological and psychological changes and is strongly associated with problems such as heart disease, cancer, skeletal fractures, liver disease, migraine headaches, anxiety, depression, metabolic syndrome and type 2 diabetes. 2,4,6 Stress-induced inflammation is likely a key factor in the development of this condition.5
A major player in the stress response is the hypothalamic-pituitary-adrenal axis or HPA axis. The hypothalamus, pituitary gland, and adrenal glands together integrate many signals in response to stressful events or stimuli. The hypothalamus is located in the brain and is the body’s main command center, maintaining homeostasis and controlling complex functions such as emotion regulation and learning.7 The pituitary gland sits directly below the hypothalamus and acts like a thermostat, constantly assessing conditions. Everything is going well. It releases hormones to help the body function properly and regulates functions such as growth, metabolism, reproduction and fluid balance. Similarly, the adrenal glands, located in the kidneys, produce hormones that regulate major functions including metabolism, immune response, and blood pressure.
Actions of the HPA Axis
The HPA axis consists of many components in the central nervous system (CNS) and peripheral tissues 1 Major players are localized to the hypothalamus (PVN), the anterior lobe of the pituitary gland, and the paraventricular nucleus of the adrenal gland. 1 Neurons in the PVN synthesize and secrete corticotropin-releasing factor (CRF), a key regulator of the HPA axis.
When a stressor is present, CRF signals the anterior pituitary gland to release adrenocorticotropic hormone (ACTH) into the circulation. Circulating ACTH targets the adrenal cortex, stimulating the synthesis and release of glucocorticoids (GCs), including cortisol, to regulate stress responses in peripheral tissues. Increased awareness and cognition, increased breathing rate and improved chances of survival including inhibition of feeding, digestion, growth and reproduction.
Glucocorticoids
Glucocorticoids are hormones that regulate physiological changes and downstream effects of the HPA axis in response to stress. They are important for homeostasis and normal functioning of vital systems that regulate growth, reproduction, immune response, behavior, and cellular metabolism. 2,6 Glucocorticoids can also have a pro- or anti-inflammatory effect on the immune system, depending on the conditions. .5 Under normal conditions, GC secretions follow a circadian rhythm, but a stressful event will override this and cause an immediate spike in GC levels. The Role of the HPA Axis in Stress
Acute stress
Short-term stress can actually be a good thing, helping to strengthen the body for future stress. The stress response is rapid, begins within seconds, and seeks to help the body survive by redirecting oxygen and nutrients to vital organs for survival, including the heart and muscles. The body needs systems to survive stress. Cytokines can activate the HPA axis by increasing GC receptor sensitivity leading to increased GC concentrations.
HPA Axis Dysfunction
Dysfunction of the HPA axis can occur when any part of the system or its target is out of balance. Because the HPA axis is highly integrated with other networks and systems, the downstream consequences of altered HPA signaling can be significant. Hyper-activation of the HPA axis may lead to higher GC levels that are implicated in underlying mechanisms: 1,3,4,6
Intestinal barrier dysfunction
Metabolic problems
Development of hepatic disease
Mental health problems stemming from the inflammatory response
Autoimmune disease
high blood pressure
Inflammation
Inflammatory signaling molecules, including cytokines, are an important component of the stress response. However, in some cases inflammation can exacerbate HPA axis dysfunction. For example, HPA axis imbalance can lead to fat accumulation around internal organs that not only contributes to cardiometabolic disorders but also increases inflammation, which worsens HPA axis dysregulation.12
Gut microbiota
Chronic stress can weaken the barrier of the gastrointestinal tract, increase intestinal permeability and trigger an inflammatory response. 13 Dysbiosis of the gut microbiome may contribute to increased cytokine levels and resulting in lower levels of short chain fatty acids (SCFAs). 13 SCFAs are formed by fermentation of indigestible carbohydrates and help maintain gut barrier integrity, In the HPA axis.13
Nutrition and Lifestyle in Regulating the HPA Axis
healthy food
Despite the urge to eat comfort food, choosing foods that are high in nutrients can help regulate the stress response. Consumption of high-fat foods, often found in the standard American diet, contributes to dysregulation of the HPA axis before weight gain begins. Specifically, an excess of saturated fatty acids can lead to fat deposits in the hypothalamus, leading to hypothalamic inflammation.
Other lifestyle modifications
Beyond eating a healthy diet and incorporating herbs and medicinal plants, developing healthy habits supports HPA axis balance. Physical exercise can reduce HPA axis activity, decrease oxidative stress and pro-inflammatory immune responses, and increase renal-adrenal function.20 Exercise may also be able to reduce diet-induced hypothalamic inflammation.7 Additionally, meditation or mindfulness practice promotes relaxation and positively affects melatonin and serotonin levels.21 Finally, developing healthy sleep habits supports HPA axis function. Keeping a consistent sleep schedule helps maintain a normal circadian rhythm that can help support natural rhythms of cortisol release and HPA axis activation.
The HPA axis works continuously to maintain body homeostasis, responding to any stressor. Eating nutrient-dense foods, using herbs and medicinal plants, and engaging in regular physical activity are effective ways to support a healthy, well-regulated HPA axis and help maintain proper functioning of the body’s stress response.
