Orchinik, M.*; Breuner, C.; Gasser, P.; Jennings, D.: Diversity and Plasticity in Corticosteroid Action.

Stressor-induced increases in plasma corticosteroid (CORT) levels produce many physiological and neurochemical responses that serve, in large part, to facilitate appropriate behavioral responses to imminent threats. The behavioral responses to CORT are varied, being time-, context- and species-specific. Comparative studies can provide insights into how a diversity of CORT receptor mechanisms, involving neuronal membranes, ligand-activated transcription factors in neuronal cytosol, and plasma corticosteroid binding globulins (CBG), contributes to the diversity of behavioral responses. Neuronal membrane-associated receptors appear to produce rapid changes in the processing of sensory or environmental information leading to acute behavioral transitions. Between species, the affinities of these receptors for CORT appears to be inversely related to basal circulating levels of corticosterone, making these receptors particularly well suited for responding to stress levels of CORT. The context specificity of rapid CORT action appears to be related to membrane receptor-mediated signaling mechanisms, particularly the pathways regulated by behaviorally relevant neuropeptides. Seasonal differences in behavioral sensitivity to stressors may be mediated not only by seasonal differences in CORT release, but by seasonal plasticity in the number CORT receptors in neuronal membranes and/or neuronal cytosol. Additional factors in the plasticity of CORT action are the poorly understood interaction of CORT with CBGs and the potential signaling activity of CBG. CBG, which regulates the circulating levels of free CORT, is regulated by multiple factors in nonmammalian species including season, gonadal steroids, and social status. In several nonmammalian species, “CBGs” bind androgens with at least as high affinity as they bind CORT. Therefore, the binding of CORT and androgens to the same molecule may reciprocally regulate the relative concentrations of free steroids, and this may be especially significant during a stress response. In order to understand the adaptive and deleterious actions of CORT, we need to consider the dynamics and plasticity of corticosteroid interaction with plasma, neuronal membrane, and intracellular binding sites.