Vitamin D Physiology

  • Vitamin D is a steroid hormone which primarily acts to increase blood calcium and phosphate concentration. It should be noted that multiple molecular subtypes of Vitamin D exist; however, only one subtype, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), has significant endocrine activity. Consequently, whenever we mention "Vitamin D" we are referring to this endocrinologically active 1,25(OH)2D3 form.
  • Overview
    • Like all steroid hormones biosynthesis of Vitamin D begins with cholesterol and is subsequently modified step-wise by a number of different enzymes. In the case of Vitamin D, these enzymes are located in different organs and so biosynthesis of Vitamin D requires intermediate molecules to traverse long distances through the circulation.
  • Step 1: Skin
    • Using energy from the solar ultraviolet light, skin modifies a metabolite of cholesterol to form cholecalciferol (D3). Additionally, D3 can also be directly absorbed form the GI System if ingested.
  • Step 2: Liver
    • Cholecalciferol (D3) is converted to 25-hydroxycholecalciferol (25(OH)D3) in the liver.
  • Step 3: Kidney
    • 25-hydroxycholecalciferol (25(OH)D3) is converted to fully active, 1,25-dihydroxycholecalciferol (1,25(OH)2D3) in the proximal tubule
  • Pathological Pathway
    • In certain pathological situations macrophages within granulomas can express the enzyme which converts 25-(OH)D3 to 1,25-(OH)D3. Certain important anti-bacterial gene products are transcribed in a Vitamin D-dependent manner and Vitamin D synthesis within a granuloma may be an attempt to achieve high transcription of these anti-bacterial genes. Sadly, however, such Vitamin D synthesis occurs in an unregulated manner and can lead to hypercalcemia in certain granulomatous diseases.
  • Vitmain D (1,25(OH)2D3) levels are regulated by modulation of the Biosynthetic Step 3, which involves renal conversion of 25(OH)D3 to 1,25(OH)2D3. Expression of the enzyme which carries out this biosynthetic step is dependent on the presence of Parathyroid Hormone (PTH); consequently, the primary controller of Vitamin D levels is in fact PTH.
  • As discussed in Parathyroid Hormone Physiology, PTH secretion is itself controlled by blood calcium concentration; thus, Vitamin D synthesis is ultimately controlled by blood calcium by proxy through PTH
  • When calcium is low, high PTH levels activate Step 3 conversion and so Vitamin D levels are increased
  • When calcium is high, low PTH levels mean low Step 3 conversion and so Vitamin D levels are reduced
  • Like all steroid hormones, Vitamin D effects its physiological effect by activating specific nuclear receptors within target cells. In general, the presence of Vitamin D increases extracellular levels of both calcium and phosphate. Vitamin D achieves this by enhancing GI absorption of ingested calcium and phosphate as well as enhancing renal resorption of filtered calcium and phosphate.