Cortisol is a steroid hormone that helps regulate the metabolic and immune pathways of our body. Cortisol belongs to the glucocorticoid class of hormones produced by a pair of adrenal glands which are located above each kidney.
Each gland is made up of an inner medulla, which secretes catecholamines, and an outer cortex. The adrenal cortex itself is divided into three zones, each one secreting a different steroid hormone.
The outermost zone is the zona glomerulosa, which secretes mineralocorticoids. Next, there’s the zona fasciculata, which secretes glucocorticoids, cortisol being the most important one. And finally, there’s the zona reticularis that secretes androgens.
Cortisol production is controlled by the hypothalamus-pituitary axis. The hypothalamus, which is at the base of the brain, secretes corticotropin releasing hormone which is sensed by the anterior, or front part of the pituitary gland.
In the anterior pituitary, the corticotropin releasing hormone binds to a surface protein on a group of pituitary cells, called corticotroph cells, and stimulates them to release adrenocorticotropic hormone, or ACTH, into the bloodstream.
Adrenocorticotropic hormone then travels to the adrenal glands, binds to receptors on the cells of the adrenal cortex, and makes them take up cholesterol from the blood.
The cells of the zona fasciculata contain the enzymes needed to convert cholesterol into cortisol. Cortisol is structurally derived from cholesterol, which is a lipid molecule, and can slip in and out of cells relatively easily.
As a result, cortisol isn’t stored - it gets secreted as it’s being produced. Normally, cortisol secretion is pulsatile throughout the day, peaking in the morning around 6am.
But cortisol is also secreted in response to various stressful stimuli - including hypoglycemia or low blood sugar, infections, caffeine, sleep deprivation, and psychological stress - like getting in a fight with your best friend.
Once it’s made, cortisol travels via the blood and binds to the glucocorticoid receptors, which are generally intracellular receptors within nearly every cell in the body.
Cortisol helps to regulate both the immune response as well as cellular metabolism. 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.
In adipose tissue, cortisol triggers lipolysis, which is the breakdown of fats for energy, which can be used by other cells throughout the body.
In the liver, it promotes gluconeogenesis, which is the production of new glucose molecules. Cortisol also increases insulin resistance in tissues, which means that insulin becomes less effective at moving glucose into cells, leading to an increase in blood glucose levels.
The increased glucose level also stimulates the release of more insulin. And, because this is similar to what happens in people with diabetes, this effect of cortisol is called diabetogenic.