Glucocorticoids, stress, and behavior: Shifting the timeframe

Miles Orchinik

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Any general model of stress will have difficulty explaining the modulation of behavior by glucocorticoids. If a stressor is defined as a perceived threat to an organism's fitness (survival and reproductive output), rather than a threat to homeostasis, behavior becomes an integral component of the stress response. But this will not resolve arguments over what stress is or whether mating is stressful to B. marinus. It may be more productive to develop an integrated model of glucocorticoid action in which corticosteroids, released in a diurnal rhythm or in response to a stressor, coordinate responses to events that disrupt equilibrium conditions. In both cases, corticosterone acts as a transitional hormone between major physiological or behavioral states, as from sleeping to activity or from courtship to escape. Corticosterone is often defined as a 'permissive' hormone, and it may act as one under basal conditions, but I make the following distinctions. A 'transitional' hormone differs from a permissive hormone, such as thyroxine, because the circulating levels of transitional hormone fluctuate greatly in response to internal or external cues, whereas permissive hormones do not. In addition, a transitional hormone exerts more transient effects than a permissive hormone. However, there are similarities between transitional and permissive hormone action: corticosteroid and thyroid hormone receptors are both ubiquitous, so most cells in the body are capable of responding to them, and the effects of both permissive and transitional hormones vary with neuroendocrine context. Neuroendocrine context is an ambiguous term, but it is quantifiable. Even concepts like individual experience or ecological constraints may be measurable, in future studies, in terms of kinetics of glucocorticoid action, variations in cellular sensitivity to corticosteroids, activity of CRH, vasopressin or monoamine systems, or the levels of fos or jun in specific brain regions. These types of neuroendocrine factors underlie the plasticity in glucocorticoid action and are likely to shape many neural and behavioral responses to corticosteroids. Glucocorticoids appear to facilitate behavioral transitions following diurnal and stress-induced release by rapidly modifying the processing of sensory information. The studies mentioned above, in which corticosterone alters the behavioral responses of male mice to the odor of an estrous female (Kavaliers et al., 1997) or the responsiveness of Taricha hindbrain neurons to tactile stimuli associated with mating (Rose et al., 1993), support this idea. In both cases, corticosteroids may produce a shift in the dominant sensory modality, redirecting the animal toward threatening external stimuli. Studies done in rats (Saphier and Feldman, 1987) also find that corticosteroids elicit rapid changes in neurophysiological responses to sensory stimulation, so this may be a common mechanism by which glucocorticoids alter brain function during exposure to a stressor. Rapid behavioral transitions induced by glucocorticoids should be regarded as key components in the stress response. In the wild, prolonged exposure to most stressors - predators, blood loss or starvation, for example - would be lethal. Given this, the rapid behavioral or metabolic actions of glucocorticoids may have obvious fitness consequences for most animals, whereas the potentially maladaptive effects of prolonged glucocorticoid exposure may be relevant primarily in stress-related disorders in humans (McEwen, 1998a). We do not yet understand how a valuable, adaptive response becomes maladaptive nor do we understand the molecular mechanisms of rapid and delayed glucocorticoid action, but greater integration of biomedical and environmental/evolutionary approaches to glucocorticoid action will help us to reach the next level of understanding.

Original languageEnglish (US)
Pages (from-to)320-327
Number of pages8
JournalHormones and Behavior
Issue number3
StatePublished - Dec 1998

ASJC Scopus subject areas

  • Endocrinology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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