Mifepristone (RU-486) causes abortion and is also used in Cushing's syndrome. Its mechanism in both indications involves:
- A Inhibition of HSD3B2 (3-beta-hydroxysteroid dehydrogenase) reducing both progesterone and cortisol synthesis
- B Competitive antagonism at progesterone receptors (PR) for abortion and glucocorticoid receptors (GR) for Cushing's syndrome ✓
- C Stimulation of endometrial prostaglandin release and adrenal androgen suppression
- D Selective blockade of the mineralocorticoid receptor in both settings
Correct answer: B. Competitive antagonism at progesterone receptors (PR) for abortion and glucocorticoid receptors (GR) for Cushing's syndrome
Explanation
Mifepristone is a potent competitive antagonist at both progesterone receptors (PR-A, PR-B) and glucocorticoid receptors (GR). In early pregnancy, PR blockade causes decidual breakdown and increases prostaglandin sensitivity (often combined with misoprostol). In Cushing's syndrome, GR blockade at peripheral tissues reduces the clinical manifestations of hypercortisolism; paradoxically, it increases cortisol and ACTH levels via negative feedback disruption. It also has some anti-androgenic and anti-mineralocorticoid activity.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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