1 a,25-dihydroxyvitamin

Bell NH, Stem PH, Pantzer E, et al. Evidence that increased circulating 1-a, 25-dihydroxyvitamin D is the probable cause for abnormal calcium metabolism in sarcoidosis. J Clin Invest 1979 64 218-225. 

Liu, Y., Chang, R.L., Cui, X.X., Newmark, H.L. and Conney, A.H. 1997. Synergistic effects of curcumin on all-trans retinoic acid- and 1 alpha,25-dihydroxyvitamin D3-induced differentiation in human promyelocytic leukemia HL-60 cells. Oncol Res 9 19-29. 

Doxercalciferol, the active ingredient in Hectorol, is a synthetic vitamin D analog that undergoes metabolic activation in vivo to form 1 (alpha),25-dihydroxyvitamin D2 (l(alpha),25-(OH)2D2), anaturally occurring, biologically active form of vitamin D2. Hectorol is available as soft... 

Gregori S, GiarratanaN, Smiroldo S, Uskokovic M, Adorini L (2002) A 1 alpha,25-dihydroxyvitamin D(3) analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice. Diabetes 51 1367-1374. 

S.A. Gardezi, C. Nguyen, P.J. Malloy, G.H. Posner, D. Feldman, S. Peleg, A rationale for treatment of hereditary vitamin D-resistant rickets with analogs of 1 alpha,25-dihydroxyvitamin D-3, J. Biol. Chem. 2001, 276, 29148-29156. 

Kolek, O.I., Hines E.R., Jones M.D., et al. 2005. 1-alpha, 25-Dihydroxyvitamin D3 upregu-lates FGF23 gene expression in bone the final link in a renal-gastrointestinal-skeletal axis that controls phosphate transport. Am. J. Physiol. Gastrointest. Liver Physiol. 289 ... 

Nemere, I., Dormanen, M.C., Hammond, M.W., et al. 1994. Identification of a specific binding protein for 1 alpha,25-dihydroxyvitamin D3 in basal-lateral membranes of chick intestinal epithelium and relationship to transcaltachia. J. Biol. Chem. 269(38) 23750-6. 

Dihydroxyvitamin (283) is the endogenous ligand for the vitamin receptor (VDR). It modulates genomic function in a tissue and developmentaHy specific manner and affects ceU proliferation, differentiation, and mineral homeostasis (74). Vitamin mobilizes calcium from the bone to maintain plasma Ca " levels. Vitamin and VDR are present in the CNS where they may play a role in regulating Ca " homeostasis. Vitamin D has potent immunomodulatory activity in vivo. 

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. 

PTH has a dual effect on bone cells, depending on the temporal mode of administration given intermittently, PTH stimulates osteoblast activity and leads to substantial increases in bone density. In contrast, when given (or secreted) continuously, PTH stimulates osteoclast-mediated bone resorption and suppresses osteoblast activity. Further to its direct effects on bone cells, PTH also enhances renal calcium re-absorption and phosphate clearance, as well as renal synthesis of 1,25-dihydroxy vitamin D. Both PTH and 1,25-dihydroxyvitamin D act synergistically on bone to increase serum calcium levels and are closely involved in the regulation of the calcium/phosphate balance. The anabolic effects of PTH on osteoblasts are probably both direct and indirect via growth factors such as IGF-1 and TGF 3. The multiple signal transduction... 

Other vitamin D analogs available in the United States include paricalcitol (19-nor-l,25-dihydroxyvitamin D2, Zemplar by Abbott Laboratories, North Chicago, IL) and doxercalciferol (1 -a-hydroxyvitamin D2, Hectoral by Bone Care International, Middleton, WI). Alfacalcidiol (1-a-hydroxyvitamin D3) is only available outside the United States. Paricalcitol has less effect on vitamin D receptors in the intestines, decreasing the effects on... 

A third and less common mechanism is production of 1,25-dihydroxyvitamin D by tumor cells (usually lymphoma), which increases GI absorption of calcium and enhances osteoclastic bone resorption. 

Effects on Vitamin D Metabolism. Lead interferes with the conversion of vitamin D to its hormonal form, 1,25-dihydroxyvitamin D. This conversion takes place via hydroxylation to 25-hydroxyvitamin D in the liver followed by 1-hydroxylation in the mitochondria of the renal tubule by a complex cytochrome P-450 system (Mahaffey et al. 1982 Rosen and Chesney 1983). Evidence for this effect comes primarily from studies of children with high lead exposure. 

Children with elevated PbB (12-120 pg/dL) were found to have significantly lower serum concentrations of the vitamin D metabolite 1,25-dihydroxy vitamin D compared with age-matched controls (p<0.001), and showed a negative correlation of serum 1,25-dihydroxyvitamin D with lead over the range of blood lead levels measured (Mahaffey et al. 1982 Rosen et al. 1980). 

The answers are 402-g, 403-a. (Hardman, pp 1529-1532, 1582-15853 Calcitriol (1,2.5-dihydroxyvitamin D) is the most active form of vitamin D. It is formed by the kidney. When the Ca blood level rises, the kidney produces 24,25-dihydroxyvitamin D, a much less active form. Vitamin D can be manufactured in the body by the action of sunlight on the skin. Its main action is to increase Ca absorption in the gut Thus, vitamin D subserves important hormonal functions in Ca homeostasis. 

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