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Physiological and Pharmacological Aspects of 24,25-Dihydroxycholecalciferol in Man

  • R. G. G. Russell
  • J. A. Kanis
  • R. Smith
  • N. D. Adams
  • M. Bartlett
  • T. Cundy
  • M. Cochran
  • G. Heynen
  • G. T. Warner
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 103)

Abstract

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).

Keywords

Chronic Renal Failure Intestinal Absorption Urine Calcium Renal Osteodystrophy Deficient Animal 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  • R. G. G. Russell
    • 1
    • 2
    • 3
  • J. A. Kanis
    • 1
    • 2
    • 3
  • R. Smith
    • 1
    • 2
    • 3
  • N. D. Adams
    • 1
    • 2
    • 3
  • M. Bartlett
    • 1
    • 2
    • 3
  • T. Cundy
    • 1
    • 2
    • 3
  • M. Cochran
    • 1
    • 2
    • 3
  • G. Heynen
    • 1
    • 2
    • 3
  • G. T. Warner
    • 1
    • 2
    • 3
  1. 1.Renal UnitChurchill HospitalOxfordUK
  2. 2.Nuffield Orthopaedic CentreOxfordUK
  3. 3.Dept. Chemical PathologyUniversity Sheffield Medical SchoolEngland

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