some perceived adaptive effects in the short-term but damaging effects if they persist. Behavior can attenuate some of the damaging effects of physiologic responses. For example, even a brief period of exercise can enhance glucose uptake by reducing the insulin resistance of muscle tissue (Perseghin et al.,1996).

The mediators of protective and damaging effects of allostatic responses are mainly adrenal steroids and catecholamines. Other hormones—such as dehydroepiandrosterone, prolactin, growth hormones, and the cytokines—also mediate adaptive or maladaptive effects, but their consequences are often specific to an organ or a system. Once the mediators are released, they produce their effects by acting on cellular receptors. The effects can be classified as primary effects; secondary outcomes, which are risk factors for disease; and tertiary outcomes, which are diseases themselves (McEwen and Seeman, 1999). The actions of the mediators adrenal glucocorticoids and catecholamines are shown in Figure 2-2. These substances act via receptors that trigger changes throughout the target cell (including changes in gene expression) that have long-lasting consequences for cell function. It is important to consider the short- and long-term consequences of hormone release for cell function. There are many examples of beneficial and adverse effects of the mediators of allostatic responses. These factors are introduced here and discussed in more detail later.

In the central nervous system, catecholamines and adrenal steroids promote the storage and retrieval of memories of events, pleasant and unpleasant, associated with arousal. However, adrenal steroids acting with excitatory amino acid neurotransmitters are associated with cognitive dysfunction involving various mechanisms that promote atrophy and, in some extreme cases, the death of neurons, particularly in the hippocampal region.

In the cardiovascular system, autonomic responses, in part because of catecholamines, promote allostasis (adaptation) by adjusting heart rate and blood pressure according to the changing demands of sleeping, waking, and physical exertion. Damaging allostatic load occurs as a result of a failure to terminate blood pressure surges efficiently. This accelerates atherosclerosis and synergizes with metabolic hormones to accelerate non-insulin-dependent diabetes.

The immune system is particularly responsive to the mediators of allostatic response. Adrenal steroids and catecholamines promote the movement of immune cells to organs or tissues where they are needed to



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