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NIH

Stress System Malfunction Could Lead to Serious, Life Threatening Disease:

Whether from a charging tiger, or an urgent deadline, the body's response to stress can be both helpful and harmful. The stress response gives us the strength and speed to ward off or flee from an impending threat. But when it persists, stress can put us at risk for obesity, heart disease, cancer, and a variety of other illnesses.

Perhaps the greatest understanding of stress and its effects has resulted from a theory by George Chrousos, M.D., Chief of the Pediatric and Reproductive Endocrinology Branch at the National Institute of Child Health and Human Development (NICHD), and Philip Gold, MD, of the Clinical Neuroendocrinology Branch at the National Institute of Mental Health (NIMH).

Introduction:

A threat to your life or safety triggers a primal physical response from the body, leaving you breathless, heart pounding, and mind racing. From deep within your brain, a chemical signal speeds stress hormones through the bloodstream, priming your body to be alert and ready to escape danger. Concentration becomes more focused, reaction time faster, and strength and agility increase. When the stressful situation ends, hormonal signals switch off the stress response and the body returns to normal.

But in our modern society, stress doesn't always let up, so we live constantly in stress, an unnatural conditions for which our body has no way to cope. Many of us now harbor anxiety and worry about daily events and relationships. Stress hormones continue to flood through the system in high levels, never leaving the blood and tissues. And so, the stress response that once gave ancient people the speed and endurance to escape life-threatening dangers runs constantly in many modern people and never shuts down.

Research now shows that such long-term activation of the stress system can have a hazardous, even lethal effect on the body, increasing risk of obesity, heart disease, depression, and a variety of other illnesses.

Much of the current understanding of stress and its effects has resulted from the theory by Drs. Chrousos and Gold. Their theory explains the complex interplay between the nervous system and stress hormones--the hormonal system known as the hypothalamic-pituitary-adrenal (HPA) axis. Over the past 20 years, Dr. Chrousos and his colleagues have employed the theory to understand a variety of stress-related conditions, including depression, Cushing's syndrome, anorexia nervosa, and chronic fatigue syndrome.

The Stress Circuit

The HPA axis is a feedback loop by which signals from the brain trigger the release of hormones needed to respond to stress. Because of its function, the HPA axis is also sometimes called the "stress circuit."

Briefly, in response to a stress, the brain region known as the hypothalamus releases corticotropin-releasing hormone (CRH). In turn, CRH acts on the pituitary gland, just beneath the brain, triggering the release of another hormone, adrenocorticotropin (ACTH) into the bloodstream. Next, ACTH signals the adrenal glands, which sit atop the kidneys, to release a number of hormonal compounds.

These compounds include epinephrine (formerly known as adrenaline), Norepinephrine (formerly known as noradrenaline) and cortisol. All three hormones enable the body to respond to a threat. Epinephrine increases blood pressure and heart rate, diverts blood to the muscles, and speeds reaction time. Cortisol, also known as glucocorticoid, releases sugar (in the form of glucose) from the body reserves so that this essential fuel can be used to power the muscles and the brain.

Normally, cortisol also exerts a feedback effect to shut down the stress response after the threat has passed, acting upon the hypothalamus and causing it to stop producing CRH.

This stress circuit affects systems throughout the body. The hormones of the HPA axis exert their effect on the autonomic nervous system, which controls such vital functions as heart rate, blood pressure, and digestion.

The HPA axis also communicates with several regions of the brain, including the limbic system, which controls motivation and mood, with the amygdala, which generates fear in response to danger, and with the hippocampus, which plays an important part in memory formation as well as in mood and motivation. In addition, the HPA axis is also connected with brain regions that control body temperature, suppress appetite, and control pain.

Similarly, the HPA axis also interacts with various other glandular systems, among them those producing reproductive hormones, growth hormones, and thyroid hormones. Once activated, the stress response switches off the hormonal systems regulating growth, reproduction, metabolism, and immunity. Short term, the response is helpful, allowing us to divert biochemical resources to dealing with the threat.