Abstract

REVSIN, Yanina  and  DE KLOET, E. Ronald. When glucocorticoids change from protective to harmful: Lessons from a type 1 diabetes animal model. Medicina (B. Aires) [online]. 2009, vol.69, n.3, pp.353-358. ISSN 0025-7680.

A fundamental question in the neuroendocrinology of stress and adaptation is how stress mediators that are crucial for resilience and health can change into harmful signals enhancing vulnerability to disease. To address this question we focus in the rodent on corticosterone as end product of the hypothalamicpituitary- adrenal (HPA) axis, which coordinates the behavioural and physiological response to stressors. The action of corticosterone is mediated by mineralocorticoid (MR) and glucocorticoid receptors (GR). The receptors are transcription factors regulating gene transcription but recently these nuclear receptors were found to mediate also rapid non-genomic actions. MR participates in the initial stress reaction important for appraisal and coping processes, while management of the later adaptive phase primarily depends on GR. Imbalance in stress mediators is a characteristic feature of a phenotype vulnerable for stressors. This concept calls for recovery of the MR:GR balance as a therapeutic strategy to promote resilience still present in the diseased brain. As an example, we discuss in this article, how the impact of excessive levels of corticosterone in a pharmacological model of type 1 diabetes can be ameliorated after a brief treatment with a GR antagonist.

Keywords : Diabetes; Stress; Stress hormones; Glucocorticoids; Glucocorticoid receptors; Molecular markers.

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