TY - JOUR
T1 - Administration of pharmacological amounts of 25(s),26-dihydroxyvitamin d3 reduces serum 1,25-dihydroxyvitamin d3 levels in rats
AU - Zerwekh, J. E.
AU - Harvey, J. A.
AU - Pak, C. Y C
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1987/11/1
Y1 - 1987/11/1
N2 - 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 μg/day for 1 week) caused a marked and significant fall in the circulating concentration of 1,25-dihydroxyvitamin D (16 ± 5 SEM us. 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 μg/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 μg/day) for 4 days and subsequently dosed with both 1,25-dihydroxyvitamin D3 (0.15 μg/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 ≪ 0.001) but significantly reduced from the value observed for rats receiving only 1,25-dihydroxyvitamin D3 (47 ± 5 us. 187 ± 38 pg/ml, P ≪ 0.001). These results suggest that 25,26-dihydroxyvitamin D3 has a previously unrecognized action in affecting the metabolism of 1,25-dihydroxyvitamin D3.
AB - 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 μg/day for 1 week) caused a marked and significant fall in the circulating concentration of 1,25-dihydroxyvitamin D (16 ± 5 SEM us. 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 μg/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 μg/day) for 4 days and subsequently dosed with both 1,25-dihydroxyvitamin D3 (0.15 μg/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 ≪ 0.001) but significantly reduced from the value observed for rats receiving only 1,25-dihydroxyvitamin D3 (47 ± 5 us. 187 ± 38 pg/ml, P ≪ 0.001). These results suggest that 25,26-dihydroxyvitamin D3 has a previously unrecognized action in affecting the metabolism of 1,25-dihydroxyvitamin D3.
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U2 - 10.1210/endo-121-5-1671
DO - 10.1210/endo-121-5-1671
M3 - Article
C2 - 3665840
AN - SCOPUS:0023548372
SN - 0013-7227
VL - 121
SP - 1671
EP - 1677
JO - Endocrinology
JF - Endocrinology
IS - 5
ER -