Some science behind the scenes

Glucocorticoids

Introduction

Corticosteroids are a class of chemicals that includes the steroid hormones that are produced in the adrenal cortex of vertebrates as well as the synthetic analogues of these hormones. Corticosteroids are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.

  • Glucocorticoids such as cortisol control carbohydrate, fat and protein metabolism, and are part of the immune response
  • Mineralocorticoids such as aldosterone control electrolyte and water levels, mainly by promoting sodium retention in the kidney.

Glucocorticoids (GC) are a class of steroid hormones that bind to the glucocorticoid receptor (GR). The name glucocorticoid (glucose + cortex + steroid) derives from their role in the regulation of the metabolism of glucose, their synthesis in the adrenal cortex, and their steroidal structure. 

Glucocorticoid effects may be broadly classified into three major categories: immunological, metabolic and fetal development. 

There may, however, be other roles.  If your glucocorticoid levels are not in balance, it has all sorts of knock on effects -  inhibition of bone formation, suppression of calcium absorption (both of which can lead to osteoporosis), delayed wound healing, muscle weakness, and increased risk of infection. These observations suggest a multitude of inter-related physiologic roles for glucocorticoids.

Immunological action

Glucocorticoids (GC)  are part of the feedback mechanism in the immune system that turns immune activity down.

They are used extensively in medicine as immunosuppressants and are used to suppress various inflammatory symptoms and so called ‘autoimmune disorders’ – see immunosuppressants however for comment on this. They are also administered as post-transplantory immunosuppressants to prevent the acute transplant rejection and graft-versus-host disease.

Being immunosuppressants they make infection more likely and also inhibit later reparative processes.  GCs have many side effects, and as a result are [I quote] “rarely sold over-the-counter”.

 And they are well known for producing hallucinations………

Hallucinations after infusion of large doses of corticosteroids. A well-known and unusually well-reported side effect.  [Article in Swedish]  Askmark H  - Neurologiska kliniken, Akademiska sjukhuset, Uppsala. PMID: 10194916

Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines Interleukin 1 (IL-1), IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, and TNF-alpha, the most important of which is IL-2. Smaller cytokine production reduces the T cell proliferation.

Glucocorticoids also suppress the humoral immunity, causing B cells to express smaller amounts of IL-2 and IL-2 receptors. This diminishes both B cell clone expansion and antibody synthesis.

Metabolic action

The name "glucocorticoid" derives from early observations that these hormones were involved in glucose metabolism.  Glucocorticoids

  • Stimulate ‘gluconeogenesis’, in particular, in the liver  - they work with enzymes to break down aminoacids and glycerol to provide glucose, our source of energy.
  • Inhibit  glucose uptake in muscle and adipose tissue -  A mechanism to conserve glucose.
  • Stimulate fat breakdown in adipose tissue: The fatty acids released by lipolysis are used for production of energy in tissues like muscle

Fetal Developmental

Glucocorticoids have multiple effects on fetal development. An important example is their role in promoting maturation of the lung and production of the surfactant necessary for extrauterine lung function.  In addition, glucocorticoids are necessary for normal brain development, by initiating terminal maturation, remodeling axons and dendrites, and affecting cell survival.

Observations

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