Alcohol, Aging and Stress

Regulation of Stress Hormone Production
by National Institute of Health

(Page 3 of 5)

Humans generally are highly adept at confronting and fending off stress - which can be defined simply as any threat to a person's physical and psychological well-being. Some of these threats are physical in nature, such as extreme temperature or extended lack of food or water. For most people, however, perceived threats to their wellbeing often are psychological in nature (work-related time pressures or stress from a relationship). Regardless of the source of the stress, the body responds by activating well-defined physiological systems that specialize in helping a person cope with the stress.

The two principal stress response systems in both humans and other animals are 1. a part of the nervous system called the sympathetic nervous system and 2. a hormone system called the hypothalamic-pituitaryadrenal (HPA) axis. Both systems enable the brain to communicate with the rest of the body. Activation of the sympathetic nervous system produces several physiological responses within seconds, such as an accelerated heart rate, increased respiration, and blood flow redistribution from the skin to the skeletal muscles. These responses facilitate the "fight or flight" behavioral response.

The Role of the HPA Axis

Activation of the HPA axis induces glucocorticoid secretion, which in turn affects a wide range of physiological responses, such as changes in blood sugar levels, and blood pressure, fat redistribution, muscle breakdown, and immune system modulation. Although these hormonal effects develop much more slowly (within hours) than those of the sympathetic nervous system, they may persist for several days and are vital to survival in the face of severe physical challenges. It is unclear, however, to what extent the activation of the sympathetic nervous system and the HPA axis helps combat psychological stress, which may not require such extensive physiological responses. The potential inappropriateness of HPA axis activation in the absence of physical stress is of special concern, because glucocorticoids exert such long-lasting effects.

The HPA axis consists of three groups of hormoneproducing cells. They reside, respectively, in the brain region called the hypothalamus; in a hormone-secreting gland called the pituitary gland (located just below the hypothalamus); and in the adrenal glands, which are situated on top of the kidneys. These groups of cells act in a coordinated fashion to control the secretion of glucocorticoid hormones from the adrenal gland into general circulation.

Glucocorticoid secretion from the adrenal glands depends directly on the release of the adrenocorticotropic hormone (ACTH) from the pituitary gland and indirectly on the release of the corticotropin-releasing hormone (CRH) from the hypothalamus. This hormone "cascade" becomes activated whenever CRH-producing nerve cells (neurons) in the hypothalamus are stimulated by neural input from other brain regions, usually in response to a stressful situation. As a result of this stimulation, these hypothalamic neurons secrete CRH into specific blood vessels located at the junction of the hypothalamus and the pituitary gland. CRH then is transported through these blood vessels to the pituitary gland (the anterior pituitary), where it stimulates specialized cells (corticotrope cells) to secrete ACTH into the bloodstream. Through the blood, ACTH is transported to the adrenal glands, where it induces certain cells to release glucocorticoids into the bloodstream. Thus, although glucocorticoid production and secretion occur in small glands located above the kidneys, these processes are ultimately controlled by the activity of various brain regions.

Glucocorticoid hormones have a wide range of regulatory effects on virtually every organ system in the body, including the central nervous system (the brain and spinal cord). Cortisol's ability to affect many body systems allows this hormone to be an effective mediator of a generalized stress response. At the same time, however, the extensive range of cortisol's effects necessitates tight regulation of the hormone's levels. This control is achieved largely through a negative feedback mechanism. Thus, cortisol itself either directly or indirectly inhibits the CRH-producing neurons in the hypothalamus and the ACTH-producing cells in the anterior pituitary that control cortisol secretion, thereby blunting overall HPA axis activity and subsequent cortisol secretion.

Although this negative feedback normally is a highly effective means of ensuring that the body is not exposed to any more cortisol than is warranted by the conditions at hand, experimental evidence has indicated that with increasing age, this regulatory mechanism becomes impaired. As discussed below, impaired cortisol negative feedback in older humans may contribute to a greater risk of alcohol-induced pathophysiology.

Impairment of the HPA Axis and Its Consequences

Researchers and clinicians have gained some insight into the consequences of extreme chronic elevation of cortisol levels from studying patients with Cushing's syndrome, a disorder that is characterized by cortisol overproduction, usually caused by an adrenal or pituitary tumor. Symptoms include diabetes, muscle weakness, skin disorders, obesity of the torso, brittle bones (osteoporosis), disrupted menstruation, high blood pressure (hypertension), and increased susceptibility to infections. Although chronic stress does not cause full-blown Cushing's syndrome, the stress-induced chronic elevation of cortisol levels may exacerbate some related disorders, such as diabetes and osteoporosis, while simultaneously decreasing a person's resistance to infectious agents.

Cushing's syndrome is not the only disorder associated with abnormal cortisol levels. Dysregulation of cortisol secretion also occurs with some neuropsychological disorders, most notably depression, Alzheimer's disease, chronic fatigue syndrome, posttraumatic stress disorder, and fibromyalgia (a recently defined syndrome of generalized pain). Researchers do not yet know, however, whether altered cortisol levels contribute to the development of these disorders or are merely a by-product of the conditions.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.