Glucocorticoid Receptor

Glucocorticoid gets their name from their effect of raising the level of blood glucose. They do this by stimulating the liver to convert fat and protein into intermediate metabolites which are ultimately converted into glucose. The most abundant Glucocorticoid is cortisol. Cortisol and other Glucocorticoids also have a potent anti-inflammatory effect on the body. They depress the immune responses, especially cell-mediated immune responses by reducing cytokine expression, reducing antibody production, inhibiting lymphocyte trafficking.  For this reason, it can be used to reduce the inflammatory destruction of the rheumatoid arthritis and other autoimmune diseases. It can also be used to prevent the rejection of transplanted organs, can be used for asthma, for HIV-AIDS. It helps to differentiae lymphoid cells and hence used in breast cancer.

Thus the physiological actions of gluciorticoids (cortisol) are to increase gluconeogenesis (generation of glucose from non-sugar carbon substrates), increase lipolysis (breakdown of fat stored in fat cells), increase protein catabolism, promote adipocyte (cells specialized in storage of fat) and reduce inflammatory responses. 

Glucocorticoids are produced by the adrenal cortex of the adrenal glands. Adrenal glands are 2 small structures situated just above the kidney. Adrenal glands consist of 2 regions;

outer layer called the “adrenal cortex” which are divided into 3 regions

(a) zona glomerulosa (b) zona fasiculata (c) zona reticularis

Cells of the zona glomerulosa produce mineralocortocoids and cells of the zona fasiculata produce the glucocortocoids.

Glucocortocoid (cortisol) is controlled by ACTH (adreno-cortocotropic hormone) produced by the anterior pituitary. ACTH secretion is in turn regulated by CRH (corticotrophin-releasing hormone) of the hypothalamus.

Most of the regulation of glucorticoid secretion is by the hypothalamus. Cortisol exerts a negative feedback on this hypothalamo-pituitary system. Cortisol acts on the hypothalamus to reduce CRH secretion. Cortisol also acts on the anterior pituitary to reduce the effect of CRH responsiveness on ACTH producing cells.

Cortisol secretion is a circadian rhythm. Plasma cortisol is highest in the morning at time of awakening and lowest around midnight. This is due to circadian Variations in CRH and ACTH.