What is the difference between glucocorticoids and mineralocorticoids?

Differences Between Glucocorticoids and Mineralocorticoids

Glucocorticoids and mineralocorticoids differ primarily in their receptor binding properties, physiological effects, and clinical applications, with glucocorticoids primarily affecting metabolism and inflammation while mineralocorticoids regulate electrolyte balance and blood pressure.

Receptor Binding and Specificity

• Glucocorticoids (like dexamethasone) bind primarily to glucocorticoid receptors (GR), while mineralocorticoids (like fludrocortisone) bind primarily to mineralocorticoid receptors (MR) 1, 2
• Hydrocortisone (cortisol), the natural glucocorticoid, can bind to both glucocorticoid and mineralocorticoid receptors, while synthetic glucocorticoids like dexamethasone bind almost exclusively to glucocorticoid receptors 1, 2
• The hippocampus contains high densities of both mineralocorticoid and glucocorticoid receptors, which may explain different neurological effects of various corticosteroids 1
• Receptor binding specificity explains why synthetic glucocorticoids like dexamethasone have minimal mineralocorticoid activity compared to natural glucocorticoids 2

Physiological Effects

Glucocorticoid Effects

• Primarily regulate metabolism, immune function, and have potent anti-inflammatory properties 1
• Increase appetite and can promote central deposition of adipose tissue 1
• Cause insulin resistance at the liver, which impairs effective management of excess calorie intake 1
• Have catabolic actions on bone and muscle, mobilizing amino acids for gluconeogenesis 1
• At high doses, can cause significant adverse effects including weight gain, hyperglycemia, and bone loss 1

Mineralocorticoid Effects

• Regulate sodium and potassium balance, water homeostasis, and blood pressure 1, 3
• Promote sodium retention and potassium excretion 1, 3
• Essential for maintaining blood pressure and preventing postural hypotension 1
• Under-replacement of mineralocorticoids is common and may predispose patients to recurrent adrenal crises 1, 3

Clinical Applications

Glucocorticoid Use

• Used primarily for their anti-inflammatory and immunosuppressive effects in various disorders 1
• First-line therapy for conditions like primary FSGS (focal segmental glomerulosclerosis) 1
• Used as adjunctive therapy in anaphylaxis (though not as first-line treatment) 1
• Used for treatment of brain metastases to reduce cerebral edema 1
• High-dose dexamethasone (approximately 0.5 mg/kg/day) has been shown to reduce the incidence of bronchopulmonary dysplasia but with potential adverse effects 1

Mineralocorticoid Use

• Used as replacement therapy in primary adrenal insufficiency, typically with fludrocortisone at doses of 50-200 μg daily 1, 3
• Not typically used for anti-inflammatory purposes 1
• Essential component of combination therapy for adrenal insufficiency along with glucocorticoid replacement 1, 3
• Higher doses (up to 500 μg daily) may be needed in children, younger adults, or during pregnancy 1, 3

Structural and Pharmacological Differences

• The potency of glucocorticoids is increased by an 11-hydroxy group, the Δ1-dehydro-configuration, and hydrophobic residues in position 16 4
• Mineralocorticoid potency is increased by 9α- or 6α-fluoro substituents 4
• Hydrophilic substituents in position 16 (like 16-hydroxylation in triamcinolone) decrease both mineralocorticoid and glucocorticoid properties 4
• Glucocorticoids can inhibit mineralocorticoid action, as demonstrated in rat studies 5

Clinical Considerations and Interactions

• Certain medications can affect metabolism of both glucocorticoids and mineralocorticoids, requiring dose adjustments 1
• Drugs to avoid with mineralocorticoids include diuretics, acetazolamide, carbenoxolone, and NSAIDs 1
• Liquorice and grapefruit juice can potentiate the mineralocorticoid effect of hydrocortisone and should be avoided 1
• Essential hypertension in a patient with primary adrenal insufficiency should be treated by adding a vasodilator, not by stopping mineralocorticoid replacement 1

Molecular Mechanisms of Action

• Both mineralocorticoid and glucocorticoid receptors act as homodimers via hormone response elements to regulate transcription 6
• Glucocorticoid receptors have been shown to modulate AP-1 and NF-κB-induced transcription by direct protein-protein interactions, a property not yet demonstrated for mineralocorticoid receptors 6
• The two isoforms of human glucocorticoid receptor (GRα and GRβ) exert opposite effects on mineralocorticoid activity 7