Regarding the mechanism of action and pharmacological effects of corticosteroids, all of the following are TRUE EXCEPT:

Explanation

## Mechanism of Corticosteroid Action ### Correct Statements (Options 0, 1, 2) **Key Point:** Glucocorticoids bind to intracellular glucocorticoid receptors (GR) in the cytoplasm. The hormone-receptor complex translocates to the nucleus and binds to glucocorticoid response elements (GREs) on DNA, modulating transcription of target genes. This is the classical genomic mechanism [cite:KD Tripathi 8e Ch 56]. **Key Point:** Mineralocorticoids (primarily aldosterone) bind to mineralocorticoid receptors in the collecting duct principal cells, upregulating epithelial sodium channels (ENaC) and Na-K-ATPase, promoting sodium reabsorption and water retention [cite:Harrison 21e Ch 335]. **Key Point:** Corticosteroids inhibit phospholipase A2 (via induction of lipocortin-1/annexin-1), reducing arachidonic acid release and synthesis of inflammatory mediators—prostaglandins, leukotrienes, and thromboxanes. This is a major anti-inflammatory mechanism [cite:KD Tripathi 8e Ch 56]. ### Incorrect Statement (Option 3) — THE ANSWER **High-Yield:** Glucocorticoids **DECREASE** insulin sensitivity and promote **HYPERGLYCEMIA**, not glucose uptake. They: - Increase hepatic gluconeogenesis (via PEPCK and G6Pase upregulation) - Decrease glucose uptake in muscle and adipose tissue - Promote lipolysis and protein catabolism - Antagonize insulin action (insulin resistance) This is why chronic corticosteroid use causes steroid-induced diabetes mellitus and hyperglycemia [cite:Harrison 21e Ch 335]. ### Summary Table | Mechanism | Effect | Correct? | |-----------|--------|----------| | Genomic (receptor-mediated transcription) | Gene modulation | ✓ | | Mineralocorticoid action (collecting duct) | Na reabsorption | ✓ | | Phospholipase A2 inhibition | Anti-inflammatory | ✓ | | Insulin sensitivity | **Decreased (not increased)** | ✗ | **Clinical Pearl:** Steroid-induced hyperglycemia is one of the most common metabolic side effects of long-term corticosteroid therapy, especially in patients with underlying glucose intolerance or diabetes.