## Corticosteroid Structure and Activity ### Essential Structural Features **Key Point:** The **11β-hydroxyl group** is essential for glucocorticoid activity. Mineralocorticoids such as aldosterone lack a free 11β-hydroxyl group — aldosterone has an 11β-oxygen involved in a hemiacetal bridge with C-18, effectively removing the free 11-OH. Compounds lacking the 11β-hydroxyl (e.g., cortisone, deoxycorticosterone) have minimal or no intrinsic glucocorticoid activity until converted to their 11β-hydroxy forms in vivo. ### Structure–Activity Relationship (SAR) | Structural Feature | Effect on Glucocorticoid Activity | Effect on Mineralocorticoid Activity | Examples | |---|---|---|---| | **11β-hydroxyl group** | **Essential** — 11-deoxy compounds have negligible GC activity | Absent (aldosterone has 11β-O in hemiacetal) | Cortisol, prednisolone, dexamethasone | | **17α-hydroxyl group** | Enhances GC potency; present in most glucocorticoids | Present in aldosterone too (not discriminating) | Cortisol, aldosterone | | **20-ketone group** | Present in all active corticosteroids | Present in all active corticosteroids | Universal | | **3-ketone group** | Present in all active corticosteroids | Present in all active corticosteroids | Universal | **High-Yield:** **Deoxycorticosterone (DOC)** lacks the 11β-hydroxyl group and is a pure mineralocorticoid with NO glucocorticoid activity. **Cortisone** (11-keto form) is inactive as a glucocorticoid until converted to **cortisol** (11β-hydroxy form) by 11β-hydroxysteroid dehydrogenase type 1 — confirming that the 11β-OH is obligatory for glucocorticoid receptor binding. **Why 17α-OH is incorrect:** The 17α-hydroxyl group is present in both cortisol (a glucocorticoid) AND aldosterone (a mineralocorticoid), so it does NOT distinguish glucocorticoids from mineralocorticoids. It is not "absent in mineralocorticoids." **Mnemonic:** **"11β-OH = GC Go"** — Without the 11β-hydroxyl, glucocorticoid activity is lost; mineralocorticoids characteristically lack a free 11β-OH. **Clinical Pearl:** This principle underlies 11β-hydroxylase deficiency (CAH): accumulation of 11-deoxycortisol and DOC — both lacking 11β-OH — means no glucocorticoid activity but strong mineralocorticoid effect, causing hypertension and hypokalemia. (Reference: KD Tripathi, *Essentials of Medical Pharmacology*, 8th ed., Chapter on Corticosteroids; Goodman & Gilman's *The Pharmacological Basis of Therapeutics*, 13th ed.)
Sign up free to access AI-powered MCQ practice with detailed explanations and adaptive learning.