Administration of pharmacological amounts of 25(s),26-dihydroxyvitamin d3 reduces serum 1,25-dihydroxyvitamin d3 levels in rats

J. E. Zerwekh, J. A. Harvey, C. Y C Pak

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1671-1677
Number of pages7
JournalEndocrinology
Volume121
Issue number5
DOIs
StatePublished - Nov 1 1987

ASJC Scopus subject areas

  • Endocrinology

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