Question

A high plasma Ca2+ level causes which one of the following conditions?

• A. Bone demineralization
• B. Increased formation of 1,25-dihydroxy cholecalciferol
• C. Decreased secretion of calcitonin
• D. Increased formation of 24,25 -dihydroxycholecalciferol

Hint:

Calcium Homeostasis:
Low $\text{Ca}^{2+} \implies$ High PTH $\rightarrow$ Active $1,25\text{-(OH)}_2\text{D}_3$.
High $\text{Ca}^{2+} \implies$ Low PTH High Calcitonin $\rightarrow$ Inactive $24,25\text{-(OH)}_2\text{D}_3$.

Answer 1

The Correct Option is D

Step 1: Understanding the Concept:
Hypercalcemia allosterically suppresses renal $1lpha$-hydroxylase while upregulating 24-hydroxylase (CYP24A1) to form inactive vitamin D catabolites.
Key Formula or Approach:
\[ \text{High Serum Ca}^{2+} \implies \text{Inhibits CYP27B1 (1}\alpha\text{-hydroxylase)} \quad \& \quad \text{Stimulates CYP24A1 (24-hydroxylase)} \longrightarrow 24,25\text{-(OH)}_2\text{D}_3 \]

Step 2: Detailed Explanation:
Renal regulation of vitamin D metabolism under high plasma calcium ($ ext{Ca}^{2+}$):
1. Hypercalcemia suppresses Parathyroid Hormone (PTH) secretion and stimulates Calcitonin secretion.
2. Low PTH and high $ ext{Ca}^{2+}$ downregulate renal $25$-hydroxyvitamin D $1\alpha$-hydroxylase (CYP27B1), shutting off active $1,25\text{-(OH)}_2\text{D}_3$ synthesis.
3. Concurrently, renal 24-hydroxylase (CYP24A1) is strongly upregulated, converting $25\text{-OH-D}_3$ into the inactive catabolic form, 24,25-dihydroxycholecalciferol ($24,25\text{-(OH)}_2\text{D}_3$).

Step 3: Final Answer:
Therefore, high plasma Ca2+ causes Increased formation of 24,25-dihydroxycholecalciferol, corresponding to option (D).