Cortisone

• Cortisone is a corticosteroid hormone that plays a vital role in regulating various physiological processes in the body.
• It is a naturally occurring hormone and is synthesized from cortisol in the adrenal cortex.
• It can also be made in the laboratory.

Cortisone structure

Cortisone 3D ball

Synthesis and Conversion

• Cortisone is derived from cortisol through a process known as interconversion.
• Cortisol is synthesized and released by the adrenal glands in response to stress and other physiological signals. Once cortisol is produced, it can be converted into cortisone through the action of an enzyme called 11-beta hydroxysteroid dehydrogenase type 1 (11β-HSD1). This conversion primarily occurs in the liver and certain target tissues.
• The interconversion of cortisol and cortisone serves to regulate the local concentration and activity of these hormones in different tissues.
• Cortisone has weaker glucocorticoid activity compared to cortisol, but it can be converted back to cortisol through the action of another enzyme, 11-beta hydroxysteroid dehydrogenase type 2 (11β-HSD2).
• This conversion is particularly important in tissues where cortisol is required for its potent anti-inflammatory and immunosuppressive effects.

Mechanism of Action

• Cortisone, like other corticosteroids, exerts its effects by binding to specific receptors inside target cells.
• These receptors, called glucocorticoid receptors, are present in many different tissues throughout the body.
• Once cortisone binds to these receptors, it triggers a cascade of cellular events that modulate gene expression and influence various biological processes.
• The primary mechanism of action of cortisone involves its interaction with glucocorticoid receptors.
• Once cortisone binds to these receptors, the cortisone-receptor complex undergoes a conformational change, allowing it to translocate into the nucleus of the cell.
• Inside the nucleus, the cortisone-receptor complex interacts with specific regions of DNA called glucocorticoid response elements (GREs) or negative glucocorticoid response elements (nGREs).
• These DNA sequences are found within the regulatory regions of target genes.
• The binding of the cortisone-receptor complex to GREs or nGREs can have various effects on gene expression, leading to both genomic and non-genomic actions.

Some of the key mechanisms of action include:

1. Anti-inflammatory Effects:

• Cortisone has potent anti-inflammatory properties. It acts by suppressing the expression of pro-inflammatory genes and inhibiting the production of inflammatory mediators, such as cytokines, chemokines, and prostaglandins. This anti-inflammatory effect helps to reduce redness, swelling, and other signs of inflammation.

2. Immunosuppressive Effects:

• Cortisone modulates the immune response by suppressing the function and activity of immune cells, such as T cells and B cells. It inhibits the production of cytokines involved in immune activation and reduces the migration of immune cells to sites of inflammation. These immunosuppressive effects are particularly important in managing autoimmune diseases and preventing organ rejection after transplantation.

3. Metabolic Effects:

• Cortisone affects various metabolic processes in the body, including carbohydrate, protein, and lipid metabolism. It promotes gluconeogenesis, the production of glucose from non-carbohydrate sources, and inhibits glucose uptake by peripheral tissues. Cortisone also facilitates the breakdown of proteins and inhibits protein synthesis. In terms of lipid metabolism, it promotes the breakdown of fats and redistributes fat stores, particularly to the face and trunk.

4. Stress Response:

• Cortisone plays a crucial role in the body's response to stress. It helps to mobilize energy reserves by increasing blood glucose levels through gluconeogenesis and glycogenolysis (the breakdown of glycogen into glucose). Cortisone also promotes vasoconstriction and increases blood pressure to ensure adequate oxygen and nutrient delivery to vital organs during stressful situations.

• It is important to note that while cortisone has potent therapeutic effects, long-term or high-dose use can lead to various side effects. These side effects arise from the systemic effects of cortisone on various tissues and can include adrenal suppression, immunosuppression, metabolic disturbances, and bone loss.

Clinical Applications

• Cortisone and its synthetic derivative, hydrocortisone (cortisol), have various clinical applications.

Some common uses of cortisone include: 1. Anti-inflammatory Treatment:

• Cortisone is used as an anti-inflammatory medication to reduce inflammation and alleviate symptoms associated with inflammatory conditions, such as:
• Arthritis: Intra-articular injections of cortisone can provide relief from joint inflammation and pain in conditions like rheumatoid arthritis and osteoarthritis.
• Dermatological Conditions: Topical cortisone creams or ointments are used to treat skin conditions, including eczema, psoriasis, and allergic reactions.
• Allergic Reactions: Systemic cortisone can be prescribed to manage severe allergic reactions, such as anaphylaxis or angioedema.

2. Adrenal Insufficiency Treatment:

• Cortisone, in the form of hydrocortisone, is used as hormone replacement therapy in individuals with adrenal insufficiency or Addison's disease.
• Adrenal insufficiency occurs when the adrenal glands do not produce enough cortisol.
• Cortisone or hydrocortisone is administered orally or through other routes to provide the necessary cortisol replacement and restore hormonal balance.

3. Immunosuppressive Therapy:

• Cortisone and other glucocorticoids are potent immunosuppressive agents.

They are used to suppress the immune response in conditions such as:

• Organ Transplantation: Cortisone is administered in combination with other immunosuppressive medications to prevent organ rejection after transplantation.
• Autoimmune Diseases: Glucocorticoids can be prescribed to manage autoimmune conditions, including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease.

• It is important to note that cortisone and other glucocorticoids are typically used for short-term or intermittent treatment due to their potential side effects when used long-term.

Side Effects

• The use of cortisone and other glucocorticoids can be associated with various side effects, especially when used in high doses or for prolonged periods.

Some common side effects include:

• Adrenal Suppression: Long-term use of cortisone can suppress the body's natural cortisol production, leading to adrenal insufficiency when the medication is discontinued.
• Immunosuppression: Cortisone can suppress the immune system, increasing the risk of infections and impairing the body's ability to fight off pathogens.
• Metabolic Effects: Prolonged use of cortisone can cause various metabolic changes, including weight gain, increased appetite, fluid retention, and elevated blood sugar levels.
• Osteoporosis: Glucocorticoids can accelerate bone loss and increase the risk of osteoporosis, leading to an increased susceptibility to fractures.
• Mood and Behavior Changes: Some individuals may experience mood swings, anxiety, insomnia, and other psychological effects with cortisone use.
• It is essential to use cortisone and other glucocorticoids under the guidance of a healthcare professional, who can monitor the dosage and duration of treatment to minimize the risk of side effects.

See Also

• Cortisol
• Glucocorticoids
• Adrenal Cortex
• Adrenal Insufficiency
• Cushing's Syndrome
• Anti-inflammatory Drugs
• Immunosuppressive Drugs
• Glucocorticoid Receptors
• Steroid Hormones

Cortisone Resources
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