Administration of pharmacological amounts of 25(s),26-dihydroxyvitamin D3 reduces serum 1,25-dihydroxyvitamin D3 levels in rats.
Pharmacological amounts of 25(s),26-dihydroxyvitamin D3 were administered to normal, vitamin D-replete rats in order to assess its pharmacological activity. Treatment with 25(s),26-dihydroxyvitamin D3 (20 micrograms/day for 1 week) caused a marked and significant fall in the circulating concentration of 1,25-dihydroxyvitamin D (16 +/- 5 SEM vs. 28 +/- 4 pg/ml, P = 0.02). This reduction of 1,25-dihydroxyvitamin D was dependent on the dose of 25,26-dihydroxyvitamin D3 administered since a 5 micrograms/day dosing regimen failed to alter serum 1,25-dihydroxyvitamin D levels. Despite the 25-66% reduction in circulating 1,25-dihydroxyvitamin D concentration produced by 25,26-dihydroxyvitamin D3 therapy, serum calcium and intestinal calcium absorption remained normal. These results suggested that 25,26-dihydroxyvitamin D has a weak agonist action or that a further metabolite that stimulates bone calcium resorption and/or intestinal calcium absorption is formed. Rats predosed with 25,26-dihydroxyvitamin D3 (20 micrograms/day) for 4 days and subsequently dosed with both 1,25-dihydroxyvitamin D3 (0.15 micrograms/day) and 25,26-dihydroxyvitamin D3 for an additional 3 days, demonstrated serum 1,25-dihydroxyvitamin D levels significantly higher than that found for control rats (47 +/- 5 vs. 25 +/- 4 pg/ml, P less than 0.001) but significantly reduced from the value observed for rats receiving only 1,25-dihydroxyvitamin D3 (47 +/- 5 vs. 187 +/- 38 pg/ml, P less than 0.001). These results suggest that 25,26-dihydroxyvitamin D3 has a previously unrecognized action in affecting the metabolism of 1,25-dihydroxyvitamin D3.
Zerwekh
J E
JE
Department of Internal Medicine, University of Texas Health Science Center, Southwestern Medical School, Dallas 75235.
Harvey
J A
JA
Pak
C Y
CY
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects; D002117:Calcitriol / Q000097:blood*; D002118:Calcium / Q000097:blood / Q000378:metabolism; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014807:Vitamin D / Q000097:blood*
D004100:Dihydroxycholecalciferols; D014807:Vitamin D; D002117:Calcitriol; C026032:25,26-dihydroxycholecalciferol; D002118:Calcium