24, 25-Dihydroxy VD3

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Background

24, 25-dihydroxyvitamin D3 [24,25(OH)2D3] is a Vitamin D (VD [1]) analogue that can inhibit some metabolic processes. It dose-dependently inhibited the intracellular 10-mM-Ca2+-evoked Ca2+-concentration-increase in enterocytes with an EC50 of 4.9 nM [2].
Vitamin D is important in calcium homeostasis, skeleton maintenance, and skeleton development. Two successive reactions are involved in the formation of VD: first the formation of 25-hydroxyvitamin D (25OHD); and second the formation of 1α, 25-dihydroxyvitamin D [1, 25(OH) 2D], the active hormonal vitamin D [3].
Ca2+ at 10 mM typically increased [Ca2+]i to a new stable value of 264 ± 16 nM from the basal value of 203 ± 13 nM. 24R, 25(OH)2D3 at concentrations from 0.2 pM to 202 nM dose-dependently inhibited the initial [Ca2+]i increase during the first 18 s (t= 300 to 318 s) and the final [Ca2+]i increase (t= 550 to 600 s), with EC50 values of 4.9 nM and 30 nM, respectively. 24R, 25(OH)2D3 at a concentration of 20 nM obtained the maximal inhibition (approximately 60%) to the Ca2+ uptake [2].
In adult female mongrel dogs with renal insufficiency, 24,25(OH)2D3 significantly decreased ionized calcium compared with the CK, without any changes in detected total calcium. This decrease was evident during the 2nd week. 24,25-(OH)2D3 treatment for an additional 4 weeks resulted in a very small additional decrease in the ionized calcium. 24,25(OH)2D3 made calcium balance in dogs slightly positive, while the calcium balance in the CK dogs was slightly negative [4].

[1]. Dennis Wagner, Heather E. Hanwell, Kareena Schnabl, et al. The ratio of serum 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 is predictive of 25-hydroxyvitamin D3 response to vitamin D3 supplementation. Journal of Steroid Biochemistry & Molecular Biology, 2011, 126:72-77.
[2]. D Larsson, L Aksnes, B Th Björnsson, et al. Antagonistic effects of 24R,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 on L-type Ca2+ channels and Na+/Ca2+ exchange in enterocytes from Atlantic cod (Gadus morhua). Journal of Molecular Endocrinology, 2002, 28:53-68.
[3]. Thomas Edouard, Abdallah Husseini, Francis H. Glorieux, et al. Serum 24,25-Dihydroxyvitamin D Concentrations in Osteogenesis Imperfecta: Relationship to Bone Parameters. J. Clin. Endocrinol. Metab., 2012, 97(4):0000-0000.
[4]. Janet M. Canterbury, George Gavellas, Jacques J. Bourgoignie, et al. Metabolic Consequences of Oral Administration of 24,25-Dihydroxycholecalciferol to Uremic Dogs. J. Clin. Invest., 1980, 65(3):571-576.