Glucocorticoids are agents that all act by activating the glucocorticoid receptor, a nuclear receptor that produces its effects via modifying gene expression. Its principle effects include an increase in blood glucose levels via multiple mechanisms including increasing hepatic gluconeogenesis, reducing peripheral glucose utilization by skeletal muscle tissue, increasing proteolysis[note 1] and lipolysis[note 2]. They also suppress the immune system via their interactions with various cytokines; for example, they inhibit the production of various cytokines (especially pro-inflammatory ones) by immune cells such as interleukin-1, interleukin-2, interleukin-3, interleukin-6, tumour necrosis factor alpha (TNF-a), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-g). Additionally they inhibit' prostaglandin and leukotriene synthesis by endothelial cells, monocytes (including macrophages) and fibroblasts. In basophils it also inhibits the IgE-dependent release of histamine.
The prototypical and natural glucocorticoid, cortisol (hydrocortisone), has glucocorticoid effects that are equally potent to its mineralocorticoid effects; many synthetic, medically-utilized glucocorticoids exert greater selectivity; e.g., betamethasone and dexamethasone both have high selectivity for the glucocorticoid receptors over the mineralocorticoid receptors.
Medically their major uses are in inflammatory/autoimmune/allergic conditions like asthma, systemic lupus erythematosus, organ rejection prevention, atopic dermatitis, sarcoidosis, etc. and several blood cancers of lymphoid origin (e.g., lymphocytic leukaemia, lymphoma and multiple myeloma) due to the fact it reduces circulating lymphocytes, eosinophils, monocytes and basophils and sensitizes them to apoptosis.
- ↑ That is, protein breakdown into free amino acids which in turn enter gluconeogenesis
- ↑ Triglyceride (fat) breakdown into fatty acids and glycerol; glycerol, being a three-carbon molecule, enters gluconeogenesis