1.25- Dihydroxyvitamin D3

FIGURE 18.37 (a) Vitamin D3 (cholecalciferol) is produced in the skin by the action of sunlight on 7-dehydrocholesterol. The successive action of mixed-function oxidases in the liver and kidney produces 1,25-dihydroxyvitamin D3, the active form of vitamin D. 

Amir, H. et ah. Lycopene and 1,25-dihydroxyvitamin D3 cooperate in the inhibition of cell cycle progression and induction of differentiation in HL-60 leukemic cells, Nutr. Cancer, 33, 105, 1999. 

Long GJ, Rosen JF. 1994. Lead perturbs 1,25 dihydroxyvitamin D3 modulation of intracellular calcium metabolism in clonal rat osteoblastic (ros 17/2.8) cells. Life Sci 54(19) 1395-1402. 

Vitamin D receptor (VDR) 1,25 dihydroxyvitamin-D3 Vitamin D response in patients affected with rickets (96) Susceptibility to osteoporosis (97) and autosomal dominant rickets disease (96)... 

Calcitriol, 1,25-dihydroxyvitamin D3, directly suppresses PTH synthesis and secretion and upregulates vitamin D receptors, which ultimately may reduce parathyroid hyperplasia. The dose depends on the stage of CKD and type of dialysis (Table 76-4). 

There has been some concern expressed regarding the use of CSFs to treat MDS patients. Because these cytokines have proliferative activity, they have the potential to induce a leukaemic transformation in the malignant clone. However, the combined use of CSFs with cytotoxic drugs such as cytosine arabinoside (ara-C) appears promising. If leukaemic clones are induced to proliferate by the cytokine, then they are killed by ara-C as they enter the cell cycle. Other forms of differentiation therapy, such as treatment with retinoids, 1,25-dihydroxyvitamin D3 and interferons, have also been tested, but results have been variable. 

Danan JL, Delorme AC, Mathieu H. 1982. Presence of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 24-hydroxylase in vitamin D target cells of rat yolk sac. J Biol Chem 257 10715-10721. 

Milde, P., Merke, J., Ritz, E., Haussler, M., and Rauterberg, E. (1989) Immuno-histochemical detection of 1,25-dihydroxyvitamin D3 receptors and estrogen receptors by monoclonal antibodies comparison of four immunoperoxidase methods. J. Histochem. Cytochem. 37,1609-1617. 

Other target organs for the action of 1,25-dihydroxyvitamin D include the kidneys, bone, muscle,vwand skin. The hormone promotes reabsorption of both Ca2+ and inorganic phosphate by kidney tubules. In bone it binds to a specific receptor where it promotes the mobilization of calcium ions. This effect may result in part from stimulation of calcium-activated ATPase of the outer membrane of bone cells. Dissolution of bone also requires the presence of parathyroid hormone (PTH), the 83-residue hormone secreted by the parathyroid gland. In women past the age of menopause and in elderly men the production of 1,25-dihydroxyvitamin D decreases.w This may be a cause of the serious bone loss (osteoporosis) frequently observed. Treatment with 1,25-dihydroxyvitamin D3 or a synthetic analog seems to be helpful to such individuals. /Xy See also Chapter 30, Section A,5. 

Certain human populations depend on dietary sources of vitamin D because of insufficient biosynthesis of the vitamin due to inadequate skin exposure to sunlight. The classic symptoms of vitamin D deficiency are rickets in children and osteomalacia in adults. 25-Hydroxyvitamin D3 is the major circulating metabolite in the blood, but the hormonally active form of the vitamin is 1,25-dihydroxyvitamin D3. The latter metabolite stimulates the intestine to absorb calcium and phosphate by two independent mechanisms and acts with parathyroid hormone to mobilize calcium, accompanied by phosphate, from the bone fluid compartment into the bloodstream. 1,25-dihydroxyvitamin D 3 is also involved in the formation of osteoclasts—giant cells that are solely responsible for the resorption of bone matrix (33). Resorption is an essential process for the development, growth, maintenance, and repair of bone. 

Dihydroxyvitamin D3 Calcium-binding protein Ostercalcin Intestine Bone... 

Chesney RW, Mazess RB, Hamstra AJ, DeLuca HF, O Reagan S. Reduction of serum-1, 25-dihydroxyvitamin-D3 in children receiving glucocorticoids. Lancet 1978 2(8100) 1123-5. 

Bergh JJ, Shao Y, Puente E, Duncan RL, Farach-Carson MC. 2006. Osteoblast Ca2+ permeability and voltage-sensitive Ca2+ channel expression is temporally regulated by 1,25-dihydroxyvitamin D3. Am J Physiol 290 C822-31. 

Vitamin D. Vitamin D is a steroidlike hormone that can be obtained from dietary sources or synthesized in the skin from cholesterol derivatives in the presence of ultraviolet light. Vitamin D produces several metabolites that are important in bone mineral homeostasis.27,31 In general, vitamin D derivatives such as 1,25 dihydroxyvitamin D3 increase serum calcium and phosphate levels by increasing intestinal calcium and phosphate absorption and by decreasing renal calcium and phosphate excretion.27,46... 

Meyer MB, Watanuki M, Kim S, et al. The human transient receptor potential vanilloid type 6 distal promoter contains multiple vitamin D receptor binding sites that mediate activation by 1,25-dihydroxyvitamin D3 in intestinal cells. Mol Endocrinol 2006 20(6) 1447-1461. 

G23. Gross, C., Stamey, T., Hancock, S., and Feldman, D., Treatment of early recurrent prostate cancer with 1,25-dihydroxyvitamin D3 (calcitriol). J. Urol. 159, 2035—2040 (1998). 

PTH, besides its well-known activity, increases the number of osteoblasts, as well as the number and activity of osteoclasts, but it reduces the activity of osteoblasts. PTH causes the activation of nonlysosomal protease calpain. Calpain attacks the osteoblasts, and provides direct access to the surface of mineralized bone for osteoclasts, with resulting increase in bone resorption. PTH activates renal D-1 -a-hydroxylase, and so it increases the conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3. Increased concentration of 1,25-dihydroxyvitamin D3... 

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