The effects of cortisol on mast cells: Cortisol and HPA axis (Part 1 of 3)

Things I’m not great at: Knowing how many posts I need to cover all the effects cortisol has on mast cells.  So this is the first of three posts on cortisol and mast cells.  Then we will get back to the tables breaking down the effects of hormones on mast cells.
Cortisol is a glucocorticoid steroid hormone with far reaching anti-inflammatory actions. It is the product of a very complex endocrine system called the HPA axis.  HPA stands for hypothalamus-pituitary-adrenal.  The hypothalamus is in the brain and the pituitary is a small structure on the edge of the hypothalamus.  The adrenal glands are above the kidneys.

The hypothalamus, pituitary and adrenal glands all release a number of hormones that affect many bodily functions. Briefly, the hypothalamus receives signals from the nervous system to make corticotropin releasing hormone (CRH).  CRH induces the pituitary to make adrenocorticotropin hormone (ACTH). ACTH induces the adrenal glands to make cortisol.

Cortisol is most well known as the stress hormone, although it has many other functions. It can be released as a response to inflammation or physical or emotional trauma.  In such instances, signals from the nervous system tell the hypothalamus that it needs to make CRH.  CRH triggers vasodilation and increased vascular permeability to allow immune cells move from the bloodstream to inflamed spaces in tissue.  CRH also triggers manufacture of ACTH, which then triggers manufacture of cortisol.

When cortisol levels are high in the adrenal gland, epinephrine can be made from norepinephrine. Cortisol is thought to regulate the enzyme that makes epinephrine at several steps in the process.  Epinephrine is also part of the stress response and participates in the fight-or-flight response.

The role for which glucocorticoids are most often prescribed is suppression of inflammation. Cortisol production is initiated very early in an inflammatory response. Cortisol counteracts vasodilation seen by many inflammatory mediators.  Cortisol also decreases vascular permeability so immune cells are not able to easily leave the bloodstream and move into tissues.  Cortisol also affects gene expression so that inflammatory products are not made as much and anti-inflammatory products are made more.  (This will be discussed in great detail when I cover how cortisol affects mast cells.)

A number of synthetic glucocorticoids, like prednisone and dexamethasone, have similar behaviors and functions. The medication hydrocortisone functions the most like cortisol in the body.  Synthetic glucocorticoids stay in the blood longer and are more bioavailable than cortisol.  The amount of cortisol produced by the body changes throughout the day in time with other functions.  Synthetic glucocorticoids cannot mimic these changes exactly and are thus inferior to cortisol.  Small changes in amount of glucocorticoid can have major effects.

References:

Oppong E, et al. Molecular mechanisms of glucocorticoid action in mast cells. Molecular and Cellular Endocrinology 2013: 380, 119-126.

Varghese R, et al. Association among stress, hypocortisolism, systemic inflammation and disease severity in chronic urticaria. Ann Allergy Asthma Immunol 2016: 116, 344-348.

Zappia CD, et al. Effects of histamine H1 receptor signaling on glucocorticoid receptor activity. Role of canonical and non-canonical pathways. Scientific Reports 2015: 5.

Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 2011: 335(1), 2-13.

2 Responses

  1. Kathy June 16, 2016 / 7:33 am

    Thanks for another great explanation.
    In the question department;
    Since my MCAS got really bad, I have started have bleeding under the skin and skin thinning like people who take steroids or Warfarin. My best guess is the heparin released by my mast cells but maybe it is something else. Will look forward to the other posts to see if I find an answer.
    Thank you for being such a great resource. You have helped me so much!
    Kathy

  2. lori June 16, 2016 / 3:12 pm

    Thank you again for providing us with such valuable information. I have learned so much from you!!!

    hugs,
    Lori

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