Question:
In pseudohypoparathyroidism, which of the following is true?
In pseudohypoparathyroidism, which of the following is true?
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PTH resistance from a loss-of-function Gsα defect cripples adenylate cyclase output.
Updated On: Jun 24, 2026
- Gain of function mutation in Gsα
- Decreased conversion of GTP to GMP
- Decreased inositol triphosphate production
- Decreased formation of cAMP
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The Correct Option is D
Solution and Explanation
Step 1: Pseudohypoparathyroidism is end-organ resistance to parathyroid hormone (PTH). PTH levels are high, but target tissues (kidney, bone) fail to respond, producing hypocalcaemia and hyperphosphataemia with elevated PTH.
Step 2: PTH signals through a G-protein coupled receptor linked to the stimulatory G protein (Gs). The alpha subunit of Gs (Gsα, encoded by GNAS) normally activates adenylate cyclase.
Step 3: In pseudohypoparathyroidism type Ia (Albright hereditary osteodystrophy), there is a loss-of-function mutation in Gsα, so adenylate cyclase is not adequately activated.
Step 4: Because adenylate cyclase converts ATP to cyclic AMP (cAMP), the defect leads to decreased generation of cAMP in response to PTH (demonstrated clinically by a blunted urinary cAMP response in the Ellsworth-Howard test).
Step 5: Evaluating the options: a gain-of-function in Gsα (option A) is wrong because the defect is loss of function; GTP-to-GMP conversion (option B) is not the relevant pathway; inositol triphosphate (option C) is the IP3/Gq pathway, not the PTH-Gs-cAMP pathway.
Conclusion: The correct answer is decreased formation of cAMP.
Step 2: PTH signals through a G-protein coupled receptor linked to the stimulatory G protein (Gs). The alpha subunit of Gs (Gsα, encoded by GNAS) normally activates adenylate cyclase.
Step 3: In pseudohypoparathyroidism type Ia (Albright hereditary osteodystrophy), there is a loss-of-function mutation in Gsα, so adenylate cyclase is not adequately activated.
Step 4: Because adenylate cyclase converts ATP to cyclic AMP (cAMP), the defect leads to decreased generation of cAMP in response to PTH (demonstrated clinically by a blunted urinary cAMP response in the Ellsworth-Howard test).
Step 5: Evaluating the options: a gain-of-function in Gsα (option A) is wrong because the defect is loss of function; GTP-to-GMP conversion (option B) is not the relevant pathway; inositol triphosphate (option C) is the IP3/Gq pathway, not the PTH-Gs-cAMP pathway.
Conclusion: The correct answer is decreased formation of cAMP.
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