Chapter 3.1 - Corticosteroid receptors and HPA-axis regulation

摘要: : The activity of the hypothalamic–pituitary–adrenal (HPA) axis has three modes operation: (1) pulsatility with intervals approximately 60 min; (2) circadian variation peak prior to onset active period; and (3) a profound activation in response physical psychological stressors. End products HPA are cortisol corticosterone, which co-ordinate, concert other components axis, body brain responses stressor thereby facilitate adaptive processes. The actions corticosteroids mediated by receptors mineralocorticoid (MR) glucocorticoid (GR) acting as gene transcription factors best investigated. This chapter addresses following aspects corticosteroid action on HPA-axis activity: First, MR binds corticosterone ten-fold higher affinity than GR. differential led concept that via homeostasis is maintained, while GR-mediated signalling facilitates their recovery from stress promotes processes preparation for future events. Second, MR- effects target core well its afferents. provides an enormous diversity action. Third, feedback varies function phase pulsatility, nature intensity depends genetic determinants expressed receptor variants polymorphisms. Fourth, during development low stable due enhanced adrenal hyporesponsiveness. Early life experience at time can program reactivity life. Fifth, molecular mechanism proceeds along two fundamentally different pathways. GR bind specific DNA motifs (glucocorticoid elements – GREs) regulatory regions like promoters exert direct control over machinery recruitment co-regulators often indispensable. mode operation mostly leads transactivation or occasionally repression transcription. involves interaction (i.e. NFκB AP-1) prevent them regulation selective outcome transrepression aimed dampen stress-induced processes. The concluded thesis imbalance may lead neuroendocrine dysregulation behavioural impairments, after passing certain threshold enhances vulnerability stress-related disorders individual genetically pre-disposed.