The Hypothalamo-Pituitary-Adrenocortical Axis: Endocrinology, Pharmacology, Pathophysiology, and Developmental Effects
Glucocorticoids exert wide ranging effects in the body which, collectively, are essential for normal growth and development and for the maintenance of homeostasis. Chronic disturbances in the circulating levels of glucocorticoids, induced pathologically (e.g., Addison’s disease and Cushing’s syndrome), surgically (adrenal resection) or pharmacologically (e.g., administration of antiinflammatory steroids), are well known to induce a plethora of unwanted effects. However, growing body of data suggests that more subtle, long-term changes in the secretion and/or activity of glucocorticoids may also have serious deleterious effects. In particular, they may predispose the organism to a variety of diseases which are endemic in the western world and also emerging in developing countries, including type 2 diabetes, hypertension, and depression. This review will consider (a) the physiological and pharmacological actions of the glucocorticoids, (b) the mechanisms that control the secretion of these steroid hormones and enable them to produce tissue-specific actions and (c) the potential role of the glucocortiocoids in the etiology of disease.