Vitamin D3
Calcitriol or Vitamin D3 or Cholecalciferol (Secosteroids) is the third major hormone involved in the regulation of calcium metabolism and skeletal remodelling is calcitriol or cholecalciferol (vitamin ‑D3) or irradiated ergosterol (vitamin ‑D2).
Cholecalciferol is ingested in the diet and also synthesized from 7-dehydrocholesterol by ultraviolet irradiation.
Synthesis of Vitamin D3
Epithelial cells of the skin synthesise the precursor of vitamin D, 7-dehydrocholesterol from acetate. Exposure to sun changes 7-dehydrocholesterol to inactive vitamin D.
After absorption or synthesis, the cholecalciferol is bound to an alpha -2 globulin (vitamin D binding protein – DBP) in the blood, transported to the liver for its conversion into 25-hydroxycholecalciferol (calcidiol) by 25- hydroxylase.
In the kidney 25‑hydroxy cholecalciferol is converted into 1, 25 dihydroxy cholecalciferol (DHCC)by a rate limiting enzyme 1-α hydroxylase. 1,25 DHCC exerts strong product feedback inhibition on 1 alpha hydroxylase in the kidney.
When Calcium is normal or in excess, kidneys produce 24,25 DHCC which is inactive.
Activation of renal hydroxylase is stimulated by Parathyroid hormone, low serum Calcium level, low serum PO4 level, prolactin and estrogen and is inhibited by hypercalcemia, high serum PO4 level and Calcitonin.
Physiological effects Vitamin D3
Following synthesis in the kidney 1, 25 DHCC is transported in a protein‑bound form which is known as transcalciferin ( a -globulin) to specific target cells in the intestine and bone.
In the intestine, it stimulates increased synthesis of vitamin-D dependent proteins such as Calcium Binding Protein (CaBP) and calmodulin by intestinal cells which contributes to increased intestinal absorption of Ca. It also promotes intestinal absorption of phosphorus.
Vitamin D3 is also necessary for osteoclastic resorption and Calcium mobilization from bone. It increases the reabsorption of Calcium from kidney.
An increase in 1, 25 DHCC inhibits the secretion of PTH. DHCC induces stem cells to differentiate into osteoclasts to promote osteolysis Calcitriol has permissive effect on PTH activity on osteoclasts