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Glucocorticoids (GCs) are the end products of the hypothalamo–pituitary–adrenocortical axis (HPA) and, via activation of the ubiquitously expressed GC receptor, influence numerous physiological processes. GCs are also involved in the regulation of basal homeostasis as well as mediating adaptive responses to stress that act to restore homeostasis. This article discusses the various factors that are important in regulating plasma and intracellular GC concentrations and describes the genomic and non-genomic mechanisms used by GCs to influence cellular processes. We describe the concept of allostatic overload associated with chronic HPA activation and the subsequent development of tissue dysfunction and disease. While allostasis is associated with acute stress and a restoration of homeostasis, chronic stress is likely to induce allostatic overload owing to the sustained activation of adaptive processes. Increased wear and tear in GC-sensitive tissues can eventually lead to tissue dysfunction and disease. Chronic elevations in GCs can also induce dysfunction or disease associated with decreased tissue function owing to the prolonged inhibitory effects of GCs or the redistribution of metabolic resource away from physiological systems not involved in restoring homeostasis. Numerous endocrine-related disorders are associated with aberrant GC levels and in terms of pathophysiology may be linked with chronic tissue-specific alterations in GC actions.

european endocrinology

The Hypothalamo–Pituitary–Adrenocortical Axis – An Overview of the Role of Glucocorticoids in the Pathophysiology of Endocrine Disorders and Perspectives for the Future