10-Keto or 25-hydroxy substitution confer equivalent in vitro bone-resorbing activity to vitamin D3.
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.
Stern
P H
PH
Horst
R L
RL
Gardner
R
R
Napoli
J L
JL
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D002112:Calcifediol / Q000031:analogs & derivatives / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002762:Cholecalciferol / Q000494:pharmacology* / Q000031:analogs & derivatives; D005333:Fetus; D066298:In Vitro Techniques; D051381:Rats; D013329:Structure-Activity Relationship
D002762:Cholecalciferol; C044520:10-keto-25-hydroxyvitamin D3; C044521:10-ketovitamin D3; D002117:Calcitriol; D002112:Calcifediol