11th April 2024

Physiology of glucocorticoids

Glucocorticoids are one of three steroids produced in the adrenal glands (zona fasciculata). The process starts with the release of corticotrophin-releasing hormone from the hypothalamus. This stimulates the production of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. ACTH has a dual function; it binds to melanocortin 2 receptors, initiating signalling cascades for steroid production (in the mitochondria) and increasing the cholesterol availability, activating HMG CoA reductase and activating hormone-sensitive lipase. Dependent on the enzymes exposed, the cholesterol can be converted into mineralocorticoids, glucocorticoids or sex hormones. Important enzymes involved in the production of glucocorticoids are cholesterol desmolase, 17a-hydroxylase, 21-hydroxylase and 11-beta-hydroxylase. The final product, cortisone, is an inactive steroid that is converted to cortisol (active form) in the liver by 11-beta hydroxysteroid dehydrogenase type 1. The release of glucocorticoids follows a pulsatile circadian pattern, with the highest concentrations found in the morning. High levels of glucocorticoids inhibit the release of CRH and ACTH, while environmental factors such as stress can stimulate release.

Cortisol has several functions within the body. It increases glucose and free fatty acids availability by activating hormone sensitive lipase (HSL), encouraging glucose production and inhibiting insulin. It plays an important role in the immune system, increasing the presence of white cells through accelerating proliferation and maturation and reducing migration and apoptosis. Though glucocorticoids have no direct effects on cell growth, the concentration of the hormone can impact the production of growth hormone via the hypothalamus-pituitary-axis, with high concentrations ultimately inhibiting its secretion.