Functions of Glucocorticoids in Stress

General Considerations. The concept that corticosteroids play a key role in the body’s responses to stress emerged from the work of Selye on the alarm reaction and the general adaptation syndrome. It is now evident that cortisol/corticosterone displays two modes of activity.

The first is a permissive or proactive role in which the steroids (1) maintain the basal activity of the HPA axis and set its threshold for responding to stress and (2) normalize the body’s response to stress by priming the body’s defense mechanisms by, for example, facilitating the effects of catecholamines on lipid and carbohydrate metabolism; upregulating the expression of receptors for inflammatory mediators; and acting centrally to aid processes underlying selection attention, the integration of sensory information, and response selection.

The second mode of cortisol/corticosterone action is suppressive or protective and enables the organism to cope with, adapt to, and recover from a stressful insult. Key to this mode are the powerful anti-inflammatory and immunosuppressive actions of the steroids that prevent the host defense mechanisms, which are activated by stress, from overshooting and damaging the organism.

Other important protective actions include the ability of the steroids to redirect the metabolism to meet energy demands during stress, to exert important effects within the brain that promote memory processes, and to impair nonessential functions such as growth and reproductive function.

The permissive actions of the steroids are evident at low physiological concentrations and are mediated at least partially, although probably not exclusively, by the high-affinity MRs. In contrast, the suppressive actions of the steroids emerge only when cortisol/corticosterone levels are raised by, for example, stress and are effected by the lower-affinity GRs.

The permissive and protective actions of GCs are complementary and enable the organism to mount an appropriate stress response and to maintain homeostasis. Dysregulation of either by genetic or environmental factors is potentially harmful and may predispose the individual to a variety of diseases that, depending on the site of the lesion, may include depression, disorders of the host defense system, osteoporosis, obesity, diabetes mellitus, hypertension, and other cardiovascular diseases.

Table 1. Response to acute and long-term elevations in serum glucocorticoids

Long-term elevations in GC production that may occur in conditions of chronic stress are particularly hazardous and may have severe deleterious effects on the body. The effects of acute and sustained elevations in serum GCs are compared in Table 1.