Hormones and the Stressed Brain

Abstract

A BSTRACT : The stress system orchestrates brain and body responses to the environment. Cortisol (in humans) or corticosterone (in rodents) are important mediators of the stress system. Their action-in concert-is crucial for individual differences in coping with other individuals, which in turn depend on genetic-and experience-related factors. The actions exerted by cortisol and corticosterone have an enormous diversity. They include the regulation of rapid molecular aggregations, membrane processes, and gene transcription. In the latter transcriptional regulation, the corticosteroid hormones have two modes of operation. One mode is mediated by high-affinity mineralocorticoid receptors (MRs), which control gene networks underlying stabilization of neuronal activity as determinant for the sensitivity to trigger immediate responses to stress organized by corticotrophin-releasing hormone (CRH)-1 receptor. Whereas disturbance of homeostasis is prevented by MR-mediated processes, its recovery is facilitated via the low-affinity glucocorticoid receptors (GRs) that require stress levels of cortisol. GRs promote in coordination with CRH-2 receptors and the parasympathetic system behavioral adaptation and enhances storage of energy and information in preparation for future events. The balance in the two stress system modes is thought to be essential for cell homeostasis, mental performance, and health. Imbalance induced by genetic modification or stressors changes specific neural signaling pathways underlying cognition and emotion. This yin-yang concept in stress regulation is fundamental for genomic strategies to understand the mechanistic underpinning of corticosteroid-induced stress-related disorders such as severe forms of depression.

Impairment of Fear Memory Consolidation in Maternally Stressed Male Mouse Offspring: Evidence for Nongenomic Glucocorticoid Action on the Amygdala

“…The actions of circulating GC are mediated by binding either to the high-affinity MR or to the low-affinity GR (De Kloet, 2004). The results shown in Figures 4 and 5A demonstrate that maternally stressed mice are much less sensitive to elevated serum GC after auditory fear conditioning than control mice.…”

Prenatal Exposure to Betamethasone Decreases Anxiety in Developing Rats: Hippocampal Neuropeptide Y as a Target Molecule

“…As behavioral problems may also occur in children exposed to severe prenatal stress or repeated administration of betamethasone (French et al, 1999(French et al, , 2004Stott, 1973), continuing research is necessary to determine the mechanisms of the behavioral side effects (Avishai-Eliner et al, 2002;Matthews, 2000;Seckl, 2000;Seckl et al, 2000;. As corticosteroids may utilize multiple pathways for their actions (Beato and Sanchez-Pacheco, 1996;De Kloet, 2004;Makara and Haller, 2001;Meijer, 2002), it is reasonable to anticipate that the mechanisms responsible for the beneficial and desired effects of prenatal betamethasone (lung maturation) are distinct from mechanisms responsible for unwanted side effects on behavior. This model may help in defining pathways of prenatal betamethasone actions and selecting those in which a specific therapeutic intervention would prevent unwanted side effects.…”

The temporal dynamics of intrahippocampal corticosterone in response to stress-related stimuli with different emotional and physical load: An in vivo microdialysis study in C57BL/6 and DBA/2 inbred mice

“…These hormones terminate the stress response by inhibitory feedback action at the level of the pituitary, hypothalamus and limbic brain areas, including the hippocampus, amygdala and septum (Herman et al, 2003). This essentially dynamic process is mediated by two corticosteroid receptor molecules, highaffinity mineralocorticoid receptors (MRs) and low-affinity glucocorticoid receptors (GRs), acting both by modifying gene transcription activity and by non-genomic mechanisms on cell signalling processes (de Kloet, 2004). The MR primarily mediates the effects of, and possibly controls, low basal circadian levels of circulating steroids, whereas the GR appears to act at stress-related levels of glucocorticoids and mediates inhibitory feedback effects on the HPA system (de Kloet et al, 1998).…”