Physiological and Pharmacological Aspects of 24,25-Dihydroxycholecalciferol in Man
1978
It is now established that the biological activity of cholecalciferol (vitamin D3) results from a series of metabolic conversions to more active compounds. (1–3) The first of these con-versions is hydroxylation of D3 to 25-hydroxycholecalciferol (25-HCC), which occurs in the liver. Further metabolism to dihydroxy metabolites (1,25-DHCC, 24,25-DHCC and 25,26-DHCC) then occurs. The synthesis of 1,25-DHCC probably takes place exclusively in the kidney (4), since its production becomes un-detectable after nephrectomy. Synthesis of 24,25-DHCC also occurs in the kidney, but possibly also in other sites such as intestine (3) and cartilage (5), both of which can convert 25-HCC to 24,25-DHCC in vitro. The site of synthesis of 25,26-DHCC is un-known. The dihydroxymetabolite which has aroused the greatest interest is 1,25-DHCC, since it appears to be the major bio-logically active form of the vitamin. Thus at low doses it promotes the intestinal absorption of calcium and phosphate in vitamin D deficient animals or birds, and it increases mobilisation of calcium from bone and heals rickets. The rate of production of 1,25-DHCC is closely controlled by various factors, and it has therefore been considered a hormone derived from the kidney which acts in concert with parathyroid hormone (PTH) and calcitonin (CT) to regulate calcium metabolism. Defective synthesis of 1,25-DHCC, despite adequate supplies of the parent vitamin D3, is thought to contribute to the abnormalities of mineral metabolism in a number of clinical disorders, including chronic renal failure (6), vitamin D-dependent rickets (7), hypoparathyroidism and pseudo-hypoparathyrodism (8).
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