Vitamin D

(1,25-(OH)₂D₃, calcitriol)

Production

• Vitamin D (dietary) converted to D₃ by photochemical reaction in skin
• D₃ converted to 25-hydroxy D₃ in liver
• 25-(OH)D transported to kidney where it is hydroxylated to 1,25-(OH)₂D or 24,25-(OH)₂D

Controls

• increased by fall in serum calcium
• increased by fall in serum phosphate
• 1-alpha-hydroxylation in kidney increased by parathyroid hormone

Others

• 1,25-(OH)₂D inhibits 25-(OH)D production (negative feedback)
• 1,25-(OH)₂D inhibits parathyroid hormone secretion through raised serum calcium levels, thereby suppressing its own production.

Actions

• Increases calcium and phosphate concentrations in blood
  • Increased reabsorption of calcium and phosphate in gut
  • Increased reabsorption of calcium in kidney
  • parathyroid hormone (PTH) dependent reabsorption of bone

Tissues Involved

• intestine
  • cytosolic/nuclear receptor
  • stimulates protein production (such as Ca⁺⁺ binding protein)
• kidney,
  • increases renal tubular absorption of calcium and phosphate
• bone
  • produces bone reabsorption
  • affect potentiated by parathyroid hormone
  • important in ordered remineralisation of bone

Disorders

• excess 1,25-(OH)₂D leading to hypercalcaemia, weakening of bone
• deficiency in 1,25-(OH)₂D causes hypocalcaemia and bone weakening
  • rickets / osteomalacia
    • failure of receptor for 1,25-(OH)₂D leads to rickets or osteomalacia (rickets =children,
      osteomalacia = adult)

• Vitamin D converted to D₃ by photochemical reaction in skin
• D₃ converted to hydroxy D₃ in liver
• 1,25-(OH)₂D inhibits 25-(OH)D production
• 25-(OH)D transported to kidney where it is hydroxylated to 1,25-(OH)₂D or 24,25-(OH)₂D
• 1a-hydroxylase here is one of major  control points on 1,25-(OH)₂D production
• 1,25-(OH)₂D inhibits PTH secretion through raised serum calcium levels, thereby suppressing its own production.
• Major target tissues are 
• intestine
  • cytosolic/nuclear receptor
  • stimulates protein production (such as Ca⁺⁺ binding protein)
  • failure of receptor for 1,25-(OH)₂D leads to rickets or osteomalacia (rickets =children,
    osteomalacia = adult)
• kidney,
  • increases renal tubular absorption of calcium and phosphate
• and bone
  • produces bone resorption
  • affect potentiated by PTH
  • important in ordered remineralisation of bone
• major problems occur from hypercalcaemia caused by excess 1,25-(OH)₂D
  • causes weakening of bone through excess resorption
• deficiency in 1,25-(OH)₂D causes hypocalcaemia and bone weakening

14.7.2 Vitamin D3 and its metabolites — control whole body calcium; permissive effects in bone

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