Variability in Glucocorticoid Sensitivity: The role of the glucocorticoid receptor

The adrenal glands are paired organs localized superomedially to the kidneys. Each gland is composed of a cortex and a medulla which are embryologically and functionally distinct. The cells in the medulla are the principal site of adrenaline production in the body. In the adrenal cortex, the adrenal steroids are synthesized. The cortex is composed of three histologically different zones, the zona glomemlosa, which is the outermost portion, the zona fasciculata and the zona reticularis, which is the innermost part. The adrenal cortex produces aldosterone, which is the principal mineralocorticoid, the glucocorticoid cortisol and the adrenal androgens. All steroid honnones produced by the adrenal cortex, are derived from cholesterol. About 80% of the cholesterol used for steroid synthesis is provided by circulating plasma lipoproteins (1- 3). The cells of steroidogenic tissues can also synthesize cholesterol de novo from acetate or mobilize intracellular cholesteryl ester pools (1-3). A series of enzymatic steps convert cholesterol into steroids with glucocorticoid, mineralocorticoid or androgen activity.