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  • Title: 10-Keto or 25-hydroxy substitution confer equivalent in vitro bone-resorbing activity to vitamin D3.
    Author: Stern PH, Horst RL, Gardner R, Napoli JL.
    Journal: Arch Biochem Biophys; 1985 Feb 01; 236(2):555-8. PubMed ID: 2982315.
    Abstract:
    The biological activities of 10-keto derivatives of vitamin D3 and 25-hydroxyvitamin D3 were determined in bone organ culture. Fetal rat limb bones prelabeled with 45Ca were incubated for 60 h with 10-keto-25-hydroxyvitamin D3, 10-keto-vitamin D3, 1,25-dihydroxyvitamin D3, 25-hydroxyvitamin D3, or vitamin D3. Resorption was quantified by release of 45Ca. Substitution of a keto group in the 10 position of the vitamin D3 molecule resulted in a compound equal in potency to 25-hydroxyvitamin D3. When a 10-keto group was substituted in the 25-hydroxy vitamin D3 molecule, the potency was increased 20- to 40-fold. In contrast, 1,25-dihydroxyvitamin D3 was 7500-fold more potent than 25-hydroxyvitamin D3. Since 10-keto-25-hydroxyvitamin D3 has a retention time close to that of 1,25-dihydroxyvitamin D3 on normal-phase HPLC eluted with isopropanol:hexane, it is a possible artifact in the assay of 1,25-dihydroxyvitamin D3. Based upon the observed relative activities of the two compounds, the concentration of 10-keto-25-hydroxyvitamin D3 would have to be greater than 0.8 ng/ml for it to interfere in the bioassay of 1,25-dihydroxyvitamin D3.
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