Glucocorticoids

Glucocorticoids are a group of steroid hormones, which are secreted by the two adrenal glands that sit like hats, one on top of each kidney. Each one has an inner layer called the medulla and an outer layer called the cortex. The adrenal cortex secretes different corticosteroid hormones: like glucocorticoids under the control of adrenocorticotropic hormone, or ACTH.

Normally the hypothalamus, located at the base of the brain, secretes corticotropin releasing hormone, known as CRH, which stimulates the anterior pituitary gland to secrete adrenocorticotropic hormone, known as ACTH. ACTH then travels to the pair of adrenal glands and binds to the ACTH receptors on adrenocortical cells. This causes the adrenocortical cells to release the glucocorticoids from the zona fasciculata, which have powerful anti-inflammatory and metabolic effects. These glucocorticoids have a negative feedback effect on the hypothalamic-pituitary-adrenal axis, meaning excess corticosteroids suppress the release of both CRH and ACTH into the circulation.

Now, once made, glucocorticoids enter the circulation and travel via the blood to reach the target cells. Steroids are lipophilic molecules, so they cross the cell membrane, enter inside the cell, and bind with a cytoplasmic receptor protein, called a ‘glucocorticoid receptor’. Now, this ‘glucocorticoid-receptor complex’ undergoes some structural changes, which allow them to enter inside the nucleus and bind with the ‘glucocorticoid response elements’ or GRE on the chromatin. Now, this induces transcription of specific mRNA that’s used to synthesize different proteins, which in turn modifies various cell functions and metabolic effects in the body.

The most important glucocorticoid in humans is cortisol, and it’s generally released during times of stress, like during an illness or starvation. Cortisol helps to regulate both the immune response as well as cellular metabolism like gluconeogenesis. With regard to the immune response, cortisol promotes an overall anti- inflammatory state by inhibiting the two main products of inflammation - prostaglandins and leukotrienes - as well as inhibiting interleukin-2 production by white blood cells.