A patient with McCune-Albright syndrome has café-au-lait spots, polyostotic fibrous dysplasia, and precocious puberty. The molecular defect is a postzygotic gain-of-function mutation in the GNAS gene encoding the Gsα subunit. Which second messenger accumulates excessively in affected tissues?
- A cGMP
- B cAMP ✓
- C DAG
- D IP3
Correct answer: B. cAMP
Explanation
The GNAS gene encodes the stimulatory G protein α subunit (Gsα). In McCune-Albright syndrome, activating mutations (e.g., R201H) impair the GTPase activity of Gsα, causing constitutive activation of adenenylyl cyclase and excessive cAMP production. cAMP drives hormone secretion and cell proliferation in multiple endocrine tissues. cGMP, DAG, and IP3 are produced by other signaling cascades not directly involving Gsα.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.